The American Association for Cancer Research (AACR) organizes an annual meeting program covering some of the most recent discoveries in cancer research. The conference aims to highlight work from the best minds in research and medicine from institutions all over the world. Oncotarget, exhibited by its publisher Impact Journals, will be participating virtually at the AACR Annual Meeting this year. 
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As of June 2020, Scopus released their latest 2019 Journal Rankings on Oncology. Oncotarget is among their highest rated (Q1) journals and ranked number one in total citations in oncology. The journal has published outstanding papers and reviews by authors including Bert Vogelstein, Peter K. Vogt, Pier Paolo Pandolfi, Arnold J. Levine, Brian Druker, and Carol Prives. Founding Oncotarget Editorial Board members include Nobel Laureates Andrew V. Schally and Gregg L. Semenza; Lasker Award recipients Alexander Varshavsky, Brian J. Druker, and Gregg L. Semenza; and 16 members of the US National Academy of Sciences. Oncotarget is indexed and archived in PubMed, PubMed Central, Scopus, EMBASE, and META (Chan Zuckerberg Initiative).

The 2021 AACR conference, a two-week online event, will take place from April 10-15 and May 17-21, 2021. Topics include population science and prevention, cancer biology, translational and clinical studies, survivorship, and advocacy. 

In 2019, Oncotarget participated in the AACR Annual Meeting at the Georgia World Congress Center in Atlanta, Georgia, USA, and "AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics," at the Hynes Convention Center in Boston, Massachusetts, USA. The total registration count from the 2019 AACR Annual Meeting was over 21,000—nearly 16,000 of which were scientific attendees from all over the world. 

Follow the Oncotarget Twitter account (@Oncotarget) for live updates about the conference using the #AACR21 hashtag.

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BUFFALO, NY - January 21, 2025 – A new #research paper was #published in Oncotarget's Volume 16 on January 20, 2025, titled “Anti-correlation of KLRG1 and PD-1 expression in human tumor CD8 T cells."

The study, authored by Dr. Steven A. Greenberg from Harvard Medical School, has discovered a potential new way to improve cancer treatment by studying two key molecules found in immune cells: KLRG1 and PD-1. Analysis of data from cancer patients and healthy individuals revealed that these molecules work in opposite ways in cancer-fighting cells, suggesting that targeting both at the same time could enhance the effectiveness of cancer immunotherapy.

“Much effort in the field of immuno-oncology has involved the study of combination therapies, including combinations involving blockade of more than one T cell inhibitory receptor.”

The immune system helps fight cancer through specialized cells called T cells. Treatments known as checkpoint inhibitors, which block proteins like PD-1, have been successful in helping these cells attack cancer. However, combining different checkpoint inhibitors has not always provided the expected improvements. 

This new research focuses on KLRG1, a lesser-known protein, and its relationship with PD-1. The findings suggest that targeting both markers simultaneously could create a stronger and more effective immune response against cancer. Most existing immunotherapy treatments focus only on blocking PD-1, which is commonly found in “exhausted” T cells that struggle to fight cancer. In contrast, KLRG1 is linked to more active, mature T cells that are better at attacking tumors. By blocking both PD-1 and KLRG1, new treatment strategies could help patients with hard-to-treat cancers, such as lung cancer, melanoma, and colorectal cancer.

KLRG1 has not been widely studied in cancer immunotherapy, but this research highlights its potential to revolutionize treatment strategies. While current combinations of checkpoint inhibitors have shown only limited improvements, using therapies that target both PD-1 and KLRG1 could lead to more significant and long-lasting benefits.

“Whereas much of the T cell inhibitory drug development efforts over the last decade have been focused on combinations of expression-correlated inhibitory receptor targets, the targeting of anti-correlated inhibitory receptors has greater potential to produce supra-additive benefit, and KLRG1 has this distinct property.”

Further studies and clinical trials are needed to explore how combining PD-1 and KLRG1 treatments could benefit different types of cancer. If successful, this strategy could open the door for the creation of new combined immunotherapies.

DOI - https://doi.org/10.18632/oncotarget.28679

Correspondence to - Steven A. Greenberg - sagreenberg@bwh.harvard.edu

Video short - https://www.youtube.com/watch?v=PME2xfyYN18

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Anti-Correlation Between KLRG1 and PD-1 in Tumor CD8 T Cells

BUFFALO, NY - January 22, 2025 – A new #review was #published in Oncotarget's Volume 16 on January 20, 2025, titled “Evolving concepts in HER2-low breast cancer: Genomic insights,
definitions, and treatment paradigms."

Researchers Whitney L. Hensing, Emily L. Podany, James J. Sears, Shaili Tapiavala, and Andrew A. Davis from the University of Missouri-KC School of Medicine and Washington University in St. Louis School of Medicine explore HER2-low breast cancer, a recently recognized type of breast cancer that is changing the way clinicians should approach treatment. The review explains what makes HER2-low breast cancer different and highlights new treatment options that are helping patients.

“Breast cancer, which has been historically classified as HER2-positive versus HER2-negative, is currently facing a paradigm shift in both the definition of HER2 status and in the existing treatment algorithms.”

Breast cancer is usually classified into two main types based on the HER2 protein: HER2-positive or HER2-negative. HER2-low breast cancer falls somewhere in between. Thanks to new targeted treatments, such as a drug called trastuzumab deruxtecan, patients with HER2-low breast cancer now have more options and better chances of responding to treatment.

The review looks at recent studies on the genetics of HER2-low breast cancer. Researchers found that these tumors are often hormone receptor (HR)-positive, meaning they respond to hormones like estrogen. Some tumors also carry a common genetic change called a PIK3CA mutation, which could affect how well treatments work. However, experts say HER2-low breast cancer is not a completely separate breast cancer type but rather an opportunity for more personalized treatment.

“Despite evidence from existing literature that HER2-low breast cancer does not represent a distinct biologic and prognostic subtype, the introduction of HER2-low expression as a therapeutic target has expanded patient eligibility for a potent class of anti-HER2 drugs, HER2-directed ADCs, with potential for significant efficacy.”

Despite these advances, diagnosing HER2-low breast cancer can still be difficult. Current testing methods are not always accurate, and different laboratories may get different results. The review calls for better detection methods to make sure patients who can benefit from these new treatments are correctly identified.

With cancer treatments becoming more personalized, the review also explains how clinicians can fit HER2-low treatments into existing guidelines to help patients. The success of targeted therapies is changing how breast cancer is treated, especially for patients whose cancer has metastasized.

In conclusion, experts believe ongoing research will continue to improve the way HER2-low breast cancer is diagnosed and treated. However, they stress the need for better detection methods and continued exploration of new therapies to help patients get the best possible care.

DOI - https://doi.org/10.18632/oncotarget.28680

Correspondence to - Andrew A. Davis - aadavis@wustl.edu

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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HER2-Low Breast Cancer: Genomic Insights and Evolving Treatment Paradigms

BUFFALO, NY - February 6, 2025 – A new #casereport was #published in Volume 16 of Oncotarget on February 5, 2025, titled “Acquired RUFY1-RET rearrangement as a mechanism of resistance to lorlatinib in a patient with CD74-ROS1 rearranged non-small cell lung cancer: A case report."

In this case report, Jenny L. Wu from Vanderbilt University School of Medicine and Wade T. Iams from Vanderbilt-Ingram Cancer Center describe a rare case of drug resistance in a patient with advanced non-small cell lung cancer (NSCLC). The patient, a 42-year-old man who had never smoked, initially responded well to lorlatinib, a targeted therapy designed to treat cancer driven by specific genetic alterations. However, after six months, his cancer began to grow again. Clinicians discovered that this was due to a new genetic change, known as the RUFY1-RET fusion. This finding highlights how cancers can adapt to treatment and the importance of ongoing genetic testing to guide therapy decisions.

NSCLC is the most common type of lung cancer, and in some cases, it is driven by genetic changes that can be targeted with specific drugs. The patient’s cancer originally had a ROS1 gene rearrangement, which made it responsive to lorlatinib. But as time went on, the cancer started to grow again, and tests revealed a new genetic alteration called RUFY1-RET fusion, which likely caused resistance to lorlatinib.

This new genetic change was identified using RNA next-generation sequencing (RNA NGS), an advanced test that can find mutations that standard genetic tests might miss. After discovering the RUFY1-RET gene fusion, the patient was treated with a combination of lorlatinib and pralsetinib, a drug that specifically targets RET gene alterations. While this combination helped control the cancer for about four months, the patient’s condition unfortunately worsened after four months.

“This is the first reported case of a RET fusion as a potential mechanism of resistance to lorlatinib, it identifies a novel RET fusion partner, and it emphasizes the importance of testing for acquired resistance mutations with both DNA and RNA at the time of progression in patients with targetable oncogenic drivers.”

Understanding cases like this can help clinicians and researchers develop more effective treatment strategies, including combination therapies that target multiple genetic changes to combat drug resistance. While the combined therapy in this case provided only temporary benefits, it offers important insights for future research and patient care, particularly for cancers that no longer respond to standard treatments.

DOI: https://doi.org/10.18632/oncotarget.28682
Correspondence to: Wade T. Iams, wade.t.iams@vumc.org

Keywords: cancer, ROS1 rearrangement, RET rearrangement, non-small cell lung cancer, targeted therapy, case report

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New Genetic Mutation Linked to Drug Resistance in Non-Small Cell Lung Cancer Patient

BUFFALO, NY - February 10, 2025 – A new #casereport was #published in Volume 16 of Oncotarget on February 5, 2025, titled “A case report of donor cell–derived hematologic neoplasms 9 years after allogeneic hematopoietic cell transplantation."

In this case report, Aleksandra Mroczkowska-Bękarciak and Tomasz Wróbel from Wroclaw Medical University describe a rare and serious complication after a stem cell transplant. The case involves a patient who, nine years after receiving a stem cell transplant for acute myeloid leukemia (AML), developed a new, aggressive blood cancer originating from donor cells. Despite receiving treatment, the disease progressed to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), ultimately leading to the patient’s death.

Stem cell transplants are a life-saving treatment for many blood cancers, including AML. While relapse of the original cancer is the most common concern, this case highlights another rare but serious complication: the development of donor cell-derived hematologic neoplasms (DCHN).

The report details the case of a 23-year-old woman who remained in remission for nearly 10 years following a successful hematopoietic stem cell transplant from an unrelated donor. However, she later developed a new form of leukemia, driven by genetic mutations in the ASXL1, SETBP1, and EZH2 genes—biomarkers linked to highly aggressive blood cancers. Over the next two years, the disease progressed despite intensive treatment, ultimately proving fatal.

This case highlights the need for continued monitoring of transplant recipients, even years after the procedure. Although DCHN is extremely rare, its occurrence raises critical questions about the process by which donor cells transform into leukemia.

Some stem cell donors may unknowingly carry genetic mutations that are harmless in their own bodies but could trigger cancer in recipients. Additionally, factors such as immunosuppressive therapy, bone marrow stress, and transplantation procedures may contribute to these rare but deadly outcomes.

“Early diagnosis and intervention are crucial to improving patient prognosis.” 

Ongoing research is focused on improving donor screening methods to help predict and prevent these complications. In the future, routine genetic testing for stem cell donors could become a standard part of the transplant process, helping clinicians identify potential risks before transplantation.

More studies are needed to fully understand why donor-derived cancers develop and how they can be prevented. With continued progress in precision medicine and genetic diagnostics, researchers aim to make stem cell transplants safer and more effective for all patients.

DOI - https://doi.org/10.18632/oncotarget.28686

Correspondence to - Aleksandra Mroczkowska-Bękarciak - omroczkowska@interia.pl

Video short - https://www.youtube.com/watch?v=G2zd0UqWzeE

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Rare Case of Donor Cell-Derived Blood Cancer Discovered Nine Years After Stem Cell Transplant

BUFFALO, NY – February 14, 2025 – A new #review was #published in Oncotarget, Volume 16, on February 12, 2025, titled “SETDB1 amplification in osteosarcomas: Insights from its role in healthy tissues and other cancer types.”

Authors Elodie Verdier, Nathalie Gaspar, Maria Eugenia Marques Da Costa, and Antonin Marchais from the Gustave Roussy Cancer Campus analyzed recent studies on a gene called SETDB1, which may play a key role in osteosarcoma, a type of bone cancer that mostly affects teenagers and young adults. Their review highlights how SETDB1 helps cancer cells grow, resist treatment, and avoid the immune system. Because of this, blocking SETDB1 could be a promising new way to treat osteosarcoma.

Osteosarcoma is a fast-growing bone cancer that is usually treated with surgery and chemotherapy. However, if the cancer spreads or returns, treatment options are very limited. Scientists are searching for new ways to stop this disease, and recent studies have found that osteosarcoma cells often have extra copies of the SETDB1 gene. This seems to make the cancer more aggressive and harder to treat.

“Whole exome sequencing of osteosarcoma samples from both diagnosis and relapses has highlighted several factors, including SETDB1, that are amplified in the most aggressive forms of the disease.”

SETDB1 is involved in epigenetics, meaning it affects how genes are turned on and off without changing the DNA itself. The review explains that SETDB1 helps tumors hide from the immune system, making it difficult for the body to fight the cancer naturally. The researchers believe that blocking SETDB1 could help the immune system recognize and attack osteosarcoma cells. Some experimental drugs that target SETDB1 are already being tested in the lab.

The review also describes how SETDB1 influences key cancer pathways, such as Wnt signaling, which helps cancer cells grow, and epithelial-mesenchymal transition (EMT), a process that allows cancer to spread. The authors suggest that combining SETDB1-blocking drugs with immunotherapy or radiation could be an effective new strategy for treating osteosarcoma.

Another key finding is that SETDB1 may help cancer cells become resistant to chemotherapy, making treatment less effective. This means that drugs targeting SETDB1 could not only slow cancer growth but also make existing treatments work better.

While more research is needed, this review brings attention to SETDB1 as a potential treatment target. Scientists hope that a deeper understanding of SETDB1 will lead to new therapies that improve survival rates for osteosarcoma patients.

DOI - https://doi.org/10.18632/oncotarget.28688

Correspondence to - Antonin Marchais - antonin.marchais@gustaveroussy.fr, and Maria Eugenia Marques Da Costa - jenny.marquescosta@gustaveroussy.fr

Video short - https://www.youtube.com/watch?v=f9WgaDoEubs

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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SETDB1 Amplification Identified as a Potential Target for New Osteosarcoma Treatment

BUFFALO, NY - February 18, 2025 – A new #researchpaper was #published in Oncotarget, Volume 16, on February 12, 2025, titled “Could Panitumumab with very low dose Capecitabine be an option as a maintenance regimen."

In this study, researchers Doaa A. Gamal, Aiat Morsy, and Mervat Omar from Assiut University Hospital, evaluated a new maintenance treatment for metastatic colorectal cancer (mCRC). Their findings suggest that a combination of two drugs—Panitumumab, a targeted therapy that blocks a protein called epidermal growth factor receptor to slow cancer growth, and low-dose Capecitabine, a chemotherapy drug that converts into 5-fluorouracil (5-FU) inside the body to stop cancer cells from growing and dividing—could help extend survival in patients with mCRC. This regimen appears to be both effective and well-tolerated, especially for patients with wild-type KRAS mCRC who had previously responded to treatment.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Standard treatment often involves a combination of chemotherapy and targeted therapies, but many patients face challenges related to treatment toxicity and resistance, which can lead to treatment interruptions. This study tested whether a lower-intensity maintenance treatment could help keep the cancer under control after initial treatment.

The study involved 25 mCRC patients with wild-type KRAS and BRAF, who first received six rounds of standard 5-FU-based chemotherapy with Panitumumab. Patients who responded well then switched to a maintenance treatment of Panitumumab every two weeks and a low, continuous dose of Capecitabine. The results showed that patients had a median progression-free survival of 18 months and a median overall survival of 45 months, indicating a strong potential benefit.

Patients with metastases detected at the same time as the primary tumor showed a longer progression-free survival than those with metastases appearing later. The treatment was also well tolerated, with only 8% of patients experiencing severe side effects such as skin rash or diarrhea, which were managed with standard treatments.

"In our research, the toxicity profile was very acceptable, and no patients needed to stop treatment or had a dose modification due to toxicity."

Finding a way to keep cancer under control while reducing side effects is a major goal in cancer treatment. While other maintenance therapies like Bevacizumab and Cetuximab have been studied, this research suggests that Panitumumab with low-dose Capecitabine could be a promising new option. Panitumumab is already an FDA-approved drug, but its role in maintenance therapy had not been extensively explored. The results of this study suggest that this combination may help delay disease progression while keeping side effects manageable, ultimately improving patients’ quality of life.

Although larger studies are needed, these findings open the door for further clinical trials to confirm the benefits of this regimen. If validated, this approach could change the standard of care for mCRC patients, particularly those who cannot tolerate more intensive chemotherapy.

DOI - https://doi.org/10.18632/oncotarget.28687

Correspondence to - Doaa A. Gamal - doaaalygamaal@gmail.com

Video short - https://www.youtube.com/watch?v=wuPSS0EdK-8

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Panitumumab with Low-Dose Capecitabine as a Maintenance Regimen: A Viable Option?

BUFFALO, NY - February 24, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on February 18, 2025, titled “Robust p53 phenotypes and prospective downstream targets in telomerase-immortalized human cells."

Researchers Jessica J. Miciak, Lucy Petrova, Rhythm Sajwan, Aditya Pandya, Mikayla Deckard, Andrew J. Munoz, and Fred Bunz from the Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine studied the tumor-suppressing protein p53, which plays a key role in preventing cancer. Their findings reveal how p53 affects cancer cell growth, treatment resistance, and potential drug targets, providing new insights that could improve future cancer therapies.

The p53 protein plays a crucial role in preventing cancer by stopping uncontrolled cell growth. However, many cancers mutate or suppress p53, allowing tumors to develop and resist treatment. In this study, researchers restored p53 function in colorectal cancer cells, which led to slower cellular growth, increased cellular aging (senescence), and greater sensitivity to radiation therapy. These findings suggest that p53 status influences cancer progression and response to treatment, making it a promising target for new therapies.

The study also examined hTERT-RPE1 cells; a type of non-cancerous human cell used in research. When the TP53 gene was disrupted in these cells, they grew faster and became more resistant to radiation, reinforcing the idea that p53 helps prevent cancerous growth.

Another key discovery was a previously unnoticed p53 mutation (A276P) found in a subset of hTERT-RPE1 cells. This mutation weakened p53’s ability to regulate certain genes but did not affect its ability to control calcium signaling, a process important for cell survival. The unexpected appearance of this mutation suggests that even non-cancerous cells can acquire genetic changes that mimic early cancer development. This insight could help scientists better understand how cancers evolve and become resistant to treatment.

"Cancers that retain wild type TP53 presumably harbor other clonal alterations that permitted their precursors to bypass p53-mediated growth suppression."

A breakthrough in the study was the identification of two new p53-regulated genes that could be important for cancer treatment. The first, ALDH3A1, helps detoxify harmful substances and may impact cancer cell resistance to oxidative stress. The second, NECTIN4, is a protein found in many aggressive cancers, including bladder and breast cancer. Notably, NECTIN4 is the target of enfortumab vedotin, an FDA-approved drug for bladder cancer. These discoveries provide new potential drug targets and could lead to improved therapies for cancers that still retain some p53 function.

In conclusion, this research highlights the critical role of p53 in cancer biology and suggests that restoring p53 function could make tumors more vulnerable to radiation and chemotherapy. The discovery of new p53-controlled genes provides new opportunities for targeted cancer therapies. With further research, these findings could lead to new precision medicine strategies that leverage p53’s natural tumor-suppressing abilities.

DOI - https://doi.org/10.18632/oncotarget.28690

Correspondence to - Fred Bunz - fredbunz@jhmi.edu

Video short - https://www.youtube.com/watch?v=Psxj3ctbTuk

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Researchers Identify New p53 Targets to Combat Cancer Growth

BUFFALO, NY - March 11, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on March 10, 2025, titled “EXPOSOMES and GENES: The duo influencing CANCER initiation and progression."

In this editorial, Drs. Uzma Saqib, Katherine E. Ricks, Alexander G. Obukhov, and Krishnan Hajela from Devi Ahilya Vishwavidyalaya (DAVV) in Indore, India, discuss how environmental factors, known as exposomes, interact with genes to influence cancer risk. The authors highlight how pollution, diet, infections, and chronic stress can trigger genetic alterations that may lead to cancer. Understanding these connections could play a crucial role in cancer prevention and public health strategies.

Genes store the instructions for how the body functions, but they can be damaged by harmful exposures. Polluted air, radiation, tobacco smoke, and processed foods can lead to DNA damage, interfering with the body’s natural ability to repair itself. Over time, these genetic changes can increase the risk of cancer development. The authors emphasize that nearly everyone is exposed to cancer risk factors daily. 

“According to the Global Air Quality Guidelines of World Health Organization (WHO), nearly all of the global population (>99%) breathes polluted air that exceeds guideline limits.”

For example, air pollution has been linked to lung cancer, while UV radiation is a leading cause of skin cancer. Processed meats contain harmful chemicals that can damage DNA, and excessive alcohol consumption has been shown to raise the risk of liver cancer by causing toxic buildup in cells. Even chronic stress and hormone imbalances can weaken the body’s natural defenses against cancer by altering key genetic pathways.

Infections also play a critical role in cancer risk. The Helicobacter pylori bacterium can cause stomach cancer by damaging stomach cells, while human papillomavirus (HPV) is strongly linked to cervical cancer. Other bacteria, viruses, and fungi can introduce genetic instability that contributes to tumor growth.

Despite these risks, scientists estimate that up to 40% of cancers could be prevented through lifestyle changes such as a healthy diet, regular exercise, and avoiding harmful exposures. Advances in research technology are helping scientists better understand how environmental factors alter genes, leading to new strategies for cancer detection and prevention.

“Understanding the exposome-gene-cancer research axis will have a significant impact on public health and the development of more effective strategies for prevention and treatment of diseases.”

The editorial underscores the urgent need for greater public awareness and policy action to reduce exposure to harmful environmental risks. As scientists continue to explore the connection between exposomes and genetic changes, their findings could revolutionize public health efforts and cancer prevention strategies.

By recognizing the long-term impact of environmental exposures, individuals, communities, and policymakers can take meaningful steps toward reducing cancer risk and promoting healthier environments for future generations.

DOI - https://doi.org/10.18632/oncotarget.28696

Correspondence to - Krishnan Hajela - hajelak@gmail.com

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How Environmental Exposures Affect Genes and Increase Cancer Risk

BUFFALO, NY – March 12, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on March 10, 2025, titled “COMETgazing – interesting insights, lessons for clinical practice and a call for more precision using the biomarkerSCOPE.”

Dr. Mangesh A. Thorat, affiliated with Queen Mary University of London, Homerton University Hospital, and King’s College London, discusses new findings suggesting that some women diagnosed with early-stage breast cancer may not need immediate surgery. The editorial is based on results from the COMET trial, which studied women with low- to intermediate-grade ductal carcinoma in situ (DCIS). The findings raise questions about the necessity of surgery and highlight the importance of more precise screening methods for DCIS, ensuring that only those who truly need treatment receive it.

Breast cancer screening programs are designed to detect cancer early, but this editorial reinforces the concern that some detected cancers may never become a real threat. The COMET trial compared two strategies for treating breast cancer: standard treatment, which includes surgery and possible additional therapy, versus active monitoring, where patients are closely observed without immediate intervention.

The results indicate that many of the invasive cancers diagnosed in the monitoring group were likely present from the start rather than developing from DCIS over time. Dr. Thorat points out that these invasive cancers were often slightly larger, but they did not appear to be aggressive. These findings challenge the assumption that immediate treatment is necessary for all cases of DCIS. Researchers estimate that at least half of the invasive breast cancers in this study either take years to progress or may never progress at all.

“The planned long-term follow-up of the trial may shed more light on the median length of lead-time and the proportion of IBCs regressing as well as DCIS progression under different lead-time assumptions.”

Current methods for evaluating DCIS rely heavily on histological grading, which has limitations. Dr. Thorat emphasizes the need for more precise tools to determine which DCIS cases require treatment. His previous research suggests that biomarkers, such as multi-clonal estrogen receptor (ER) expression and tumor-infiltrating lymphocytes (TILs), may help predict which DCIS cases are truly at risk of becoming invasive.

The editorial also highlights that many women prefer to avoid surgery when possible. In a related study, only 52% of patients in the standard care group followed through with it, indicating that more individuals are willing to consider alternatives to surgery. This fact underscores the importance of developing accurate biomarkers to guide treatment decisions and ensure that patients receive appropriate care without unnecessary interventions.

As researchers continue to follow patients from the COMET trial, they hope to learn more about how invasive breast cancers behave over time. Finally, Dr. Thorat encourages clinicians and scientists to rethink breast cancer treatment and develop better ways to identify which patients truly need surgery—and which do not.

DOI - https://doi.org/10.18632/oncotarget.28698

Correspondence to - Mangesh A. Thorat - m.thorat@qmul.ac.uk

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Rethinking Breast Cancer Screening: New Insights on Overdiagnosis

BUFFALO, NY - March 18, 2025 – A new precision oncology paper was #published in Oncotarget, Volume 16, on March 12, 2025, titled “Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine: Bringing next-generation precision oncology to patients."

Led by Oncotarget Editor-in-Chief Dr. Wafik S. El-Deiry and a global team of researchers, this special publication highlights the groundbreaking work of the Worldwide Innovative Network (WIN) Consortium, a global collaboration dedicated to transforming cancer care through personalized medicine. By leveraging artificial intelligence (AI), molecular profiling, and innovative clinical trials, WIN is helping clinicians tailor treatments to each patient’s unique cancer profile—moving beyond the traditional one-size-fits-all approach.

The WIN Consortium is a fast-moving, non-profit organization bringing together nearly 40 academic, industry, and research institutions, along with patient advocacy groups, across 18 countries and five continents. Founded in 2010 in France by Dr. John Mendelsohn (MD Anderson Cancer Center) and Dr. Thomas Tursz (Gustave Roussy), WIN has been led by different renowned experts. Currently under Dr. El-Deiry’s leadership, WIN continues to break barriers in cancer research, ensuring cutting-edge treatments reach patients worldwide.

“The WIN global consortium is ready to take up the challenge by bringing the best possible Precision Oncology trial to patients.”

One of WIN’s most significant contributions is the development of N-of-1 clinical trials, a revolutionary approach that personalizes cancer treatment based on a patient’s specific tumor characteristics. Unlike traditional trials that test drugs on large groups, N-of-1 trials focus on finding the best therapy for an individual patient using AI-driven algorithms, genomic analysis, and real-world data. WIN’s WINTHER trial was one of the first to use both DNA and RNA analysis to match patients with the most effective therapies, while the WINGPO trial builds on this approach by integrating AI and liquid biopsies to refine treatment selection. These innovations are helping clinicians make more precise treatment decisions and improving outcomes for cancer patients.

While advancing research, the WIN Consortium is also addressing major challenges in precision oncology, including drug accessibility, regulatory barriers, and disparities in global healthcare. By working closely with governments, pharmaceutical companies, and advocacy organizations, WIN is aiming to ensure that life-saving treatments are accessible to all patients, regardless of location or financial status.

WIN’s mission is clear: to accelerate the future of precision oncology by delivering the latest scientific advancements into real-world cancer care. As the field continues to evolve, WIN remains at the forefront, developing next-generation trials and leveraging AI-driven insights to improve patient outcomes. Through global collaboration and groundbreaking research, the WIN Consortium is shaping a future where every cancer patient receives the most effective, personalized treatment possible.

DOI - https://doi.org/10.18632/oncotarget.28703

Correspondence to - Wafik S. El-Deiry - wafik@brown.edu

Video short - https://www.youtube.com/watch?v=XAdYfFoMvUM

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WIN Consortium Leading the Future of Precision Cancer Medicine

BUFFALO, NY - March 21, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on March 13, 2025, titled “No disease left behind."

In this editorial, Dr. Muzamil Arshad from the University of Chicago Medical Center and colleagues highlight a growing concern in cancer care: radiotherapy may leave behind microscopic cancer even when scan images suggest the tumor is gone. The authors argue that this “residual disease” is more common than expected and is linked to worse long-term outcomes. Their perspective calls for a rethinking of how treatment success is judged and how cancer is followed up after therapy.

Radiotherapy, especially a form known as stereotactic ablative radiotherapy (SABR), is widely used to treat cancers in the lung, liver, prostate, and other organs.  SABR delivers high-dose radiation with outstanding precision and often shows excellent results on scans. However, the authors highlight that relying only on imaging may not provide a complete picture. Months or even years later, follow-up biopsies frequently reveal cancer cells that scan imaging tests were unable to identify.

“Residual cancer is identified on histology in 40% of lung, 57–69% of renal cell, 7.7–47.6% of prostate and 0–86.7% of hepatocellular carcinoma.”

This gap between what scans show and what tissue analysis finds can have serious consequences. Studies across several cancer types have shown that patients with residual disease—even if small—are more likely to experience cancer recurrence and shorter survival. This pattern holds true for rectal, cervical, prostate, and liver cancers, among others. In some cases, not  destroying the tumor completely may allow it to spread to distant organs.

The authors point out that a complete response on scan imaging does not necessarily indicate the complete disappearance of the tumor. This mismatch can mislead both clinicians and patients into thinking treatment was more successful than it truly was. The editorial encourages more regular use of biopsy-based tests and new strategies to increase the true effectiveness—or “ablative power”—of SABR.

They also discuss promising approaches to improve outcomes, including increasing radiation doses and combining radiotherapy with other therapies, such as immune checkpoint inhibitors. While some trials have shown better tumor control with these combinations, results have not been consistent, and more research is needed to refine these strategies.

In summary, this editorial encourages the cancer care community to look beyond the scan images. Residual cancer may remain even when imaging looks clear, and recognizing this hidden threat is key to improving long-term outcomes. The goal is not just to shrink tumors on screen but to fully eliminate the disease.

DOI - https://doi.org/10.18632/oncotarget.28700

Correspondence to - Muzamil Arshad - muzamil.arshad@uchicagomedicine.org

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Clear Scans Can Be Misleading: Residual Cancer Linked to Worse Outcomes

BUFFALO, NY - April 2, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 21, 2025, titled “NSD2-epigenomic reprogramming and maintenance of plasma cell phenotype in t(4;14) myeloma."

Researchers Andrea Gunnell, Scott T. Kimber, Richard Houlston, and Martin Kaiser from The Institute of Cancer Research, London, studied how a gene called NSD2 affects the behavior of multiple myeloma (MM) cells. Their findings reveal that NSD2 plays a key role in helping cancer cells retain their identity as plasma cells—white blood cells that normally help the immune system fight infections. This discovery could shape future treatment strategies for patients with a high-risk form of MM known as t(4;14) myeloma.

Multiple myeloma is a type of blood cancer that begins in plasma cells found in the bone marrow. About 20% of patients have a genetic change called t(4;14), which makes the NSD2 gene highly active. The research team compared two types of myeloma cells: one with high NSD2 activity and one where NSD2 was turned off. They found that when NSD2 is active, it changes how DNA is folded and how genes are switched on or off, especially genes that help the cells act like plasma cells. When NSD2 was turned off, important markers like CD38 were reduced, and other genes normally silent in plasma cells were activated.

The study indicated that NSD2 does not directly affect the main genes responsible for plasma cell creation. Instead, it influences many other genes that help maintain the cancer cell’s identity, which contributes to cancer growth and survival. 

The researchers also observed physical changes in the cancer cells. Cells with active NSD2 looked and behaved more like typical plasma cells, while cells without NSD2 appeared more immature and lost important surface markers. These changes were linked to differences in how the DNA was organized inside the cells.

These findings are especially important as new drugs are being developed to block NSD2. The study suggests that turning off NSD2 could change how MM cells respond to existing treatments. For example, if NSD2 is blocked and CD38 levels drop, the change might affect therapies that target CD38. However, the rise of other immune-related genes might make certain immunotherapies more effective.

“Identifying the biological consequences of NSD2 over-expression in MM is not only relevant to informing new therapeutic interventions through indirect targeting of downstream effectors, but also to anticipate possible consequences of targeting NSD2 directly.”

In summary, this study shows how NSD2 helps myeloma cells keep their cancerous identity by reorganizing the DNA and influencing gene activity. Understanding this role could help researchers design better treatment approaches and possibly overcome resistance to current therapies in t(4;14) myeloma.

DOI - https://doi.org/10.18632/oncotarget.28706

Correspondence to - Andrea Gunnell - andrea.gunnell@icr.ac.uk

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NSD2 Gene Drives Cancer Cell Identity in Multiple Myeloma

BUFFALO, NY - April 4, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 27, 2025, titled “Imipridones ONC201/ONC206 + RT/TMZ triple (IRT) therapy reduces intracranial tumor burden, prolongs survival in orthotopic IDH-WT GBM mouse model, and suppresses MGMT."

Researchers from Brown University, led by first author Lanlan Zhou and corresponding author Wafik S. El-Deiry, have shown that combining a new class of drugs called imipridones with standard glioblastoma treatments significantly improves outcomes in mice. The study tested ONC201 and its analog ONC206 in combination with radiation therapy and the chemotherapy drug temozolomide (TMZ), a regimen referred to as IRT. This triple therapy slowed tumor growth and extended survival in a mouse model of glioblastoma, offering a potential new strategy for one of the most aggressive and treatment-resistant brain cancers.

Glioblastoma is a fast-growing brain tumor with a poor prognosis and limited treatment options. Standard care typically includes surgery, radiation, and TMZ, but most patients still face a short life expectancy. While ONC201 and ONC206 are currently being studied in clinical trials as single agents, there has been limited information on how they interact with standard therapies. This study is the first to show that both drugs work synergistically with radiation and TMZ, strengthening their overall effects.

The results showed that in both laboratory-grown tumor cells and mice, the triple therapy significantly slowed cancer cell growth, reduced tumor size, and prolonged survival compared to using any single or double treatment. Mice treated with IRT lived an average of 123 days, with some surviving more than 200 days—far longer than the 44 to 103 days observed with other treatment combinations. In addition to directly killing tumor cells, ONC201 and ONC206 lowered the expression of MGMT, a protein that helps tumors resist chemotherapy, making the treatment more effective.

The researchers also found that the triple therapy reshaped the tumor environment. It decreased levels of harmful molecules that promote tumor growth and immune evasion while increasing signals that activate the immune system. This dual action—directly attacking tumors and boosting immune responses—adds to the potential impact of this treatment approach.

“Overall, our preclinical findings support further exploration of the ONC201 and ONC206 IRT regimen as a potential treatment for GBM and diffuse gliomas with H3K27M mutations.”

While these findings are based on preclinical mouse models, they offer strong support for advancing this triple therapy to clinical trials. ONC201 and ONC206 are promising due to their ability to cross the blood-brain barrier and enhance the effects of standard treatment. This combination could lead to more effective therapies for glioblastoma and other hard-to-treat brain tumors.

DOI - https://doi.org/10.18632/oncotarget.28707

Correspondence to - Wafik S. El-Deiry - wafik@brown.edu

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Triple Therapy Slows Glioblastoma Growth and Extends Survival in Preclinical Study

BUFFALO, NY - April 8, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on April 4, 2025, titled “Deep learning-based uncertainty quantification for quality assurance in hepatobiliary imaging-based techniques."

Dr. Yashbir Singh from Mayo Clinic and his colleagues discussed how artificial intelligence (AI) can improve liver imaging by recognizing when it might be wrong. This approach, called “uncertainty quantification,” helps clinicians better detect liver cancer and other diseases by pointing out areas in medical scans that need a second look. The authors explain how these AI tools could make imaging results more accurate and reliable, which is especially important when diagnosing serious conditions like liver tumors.

Liver and bile duct imaging is difficult because of the organ’s complex structure and differences in image quality. Even skilled radiologists can struggle to identify small or hidden tumors, especially in patients with liver damage or scarring. The editorial explains how new AI models not only read medical images but also measure their own confidence. When the AI system is unsure, it can alert clinicians to take a closer look. This extra layer of information can reduce missed diagnoses and improve early detection of liver cancer.

One of the most advanced tools described in the editorial is called AHUNet (Anisotropic Hybrid Network). This AI model works with both 2D and 3D images and can highlight which parts of a scan it is most confident about. It performed well when measuring the entire liver and showed how its confidence dropped when scanning smaller or multiple lesions. This feature helps clinicians know when more testing or review is needed.

The authors also looked at other AI models used in liver imaging. Some tools were able to analyze liver fat using ultrasound images and give clinicians both a result and a confidence score. Others improved the speed and accuracy of liver magnetic resonance imaging (MRI) scans, helping to create clear images in less time. These advancements could help hospitals work faster and provide better care.

The editorial highlights how this technology can be especially helpful in smaller clinics. If they do not have liver specialists, they could still use AI systems that flag uncertain results and send them to larger centers for review. Such an approach could improve care in rural or less-resourced areas.

“Radiology departments should develop standardized reporting templates that incorporate uncertainty metrics alongside traditional imaging findings.”

By using AI tools that know when to second-guess themselves, clinicians may soon have more reliable methods for detecting liver cancer and monitoring liver disease. The authors suggest that uncertainty-aware AI may soon become a vital part of everyday medical imaging, supporting faster and more accurate decisions in liver disease care.

DOI: https://doi.org/10.18632/oncotarget.28709

Correspondence to: Yashbir Singh — singh.yashbir@mayo.edu

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Keywords: cancer, deep learning, uncertainty quantification, radiology, hepatobiliary imaging

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AI That Measures Its Own Uncertainty Could Improve Liver Cancer Detection

BUFFALO, NY - April 11, 2025 – A new research perspective was published in Oncotarget, Volume 16, on April 4, 2025, titled “GSK3β activation is a key driver of resistance to Raf inhibition in BRAF mutant melanoma cells."

In this work, first author Diana Crisan and corresponding author Abhijit Basu from the University Hospital Ulm led a team that presents experimental evidence pointing to the protein GSK3β as a key contributor to drug resistance in melanoma. Their findings suggest that GSK3β becomes increasingly active in cancer cells during treatment, helping them survive and adapt despite ongoing therapy with BRAF inhibitors.

Melanoma is a type of skin cancer in which nearly half of patients have mutations in the BRAF gene that accelerate tumor growth. While treatments targeting BRAF, known as BRAF inhibitors, initially work well, tumors often find ways to fight back. This research perspective explores how GSK3β, a protein involved in metabolism and cell survival, becomes more active in melanoma cells that develop resistance to BRAF inhibitors.

Researchers treated melanoma cells with a common BRAF mutation using Dabrafenib, a widely used BRAF inhibitor. Over time, the cancer cells developed resistance and showed a marked increase in GSK3β levels. This pattern was confirmed across multiple melanoma cell models, suggesting that the finding is consistent and reliable.

Importantly, the researchers observed that treating resistant cancer cells with a GSK3β inhibitor significantly reduced their growth. This result suggests that blocking this protein could restore sensitivity to treatment, highlighting GSK3β as a promising therapeutic target and supporting the idea of combining GSK3β inhibitors with existing melanoma therapies.

“Remarkably, treatment of BRAFi-resistant melanoma cells with the GSK3 inhibitor LY2090314 for three weeks could overcome resistance and significantly decreased melanoma cell growth, confirming the causal role of GSK3 activation for BRAFi resistance development.”

The research perspective adds to ongoing efforts to understand and overcome melanoma drug resistance. It shows that resistance is not driven only by genetic mutations but may also involve adaptive changes in the cell’s internal signaling and survival mechanisms. By identifying GSK3β as a potential contributor, the authors offer a new direction for improving the durability of targeted treatments in melanoma.

As research continues, GSK3β may be a critical factor in the long-term success of melanoma therapy, particularly for patients who have stopped responding to standard BRAF-targeted drugs.

Continue reading: DOI: https://doi.org/10.18632/oncotarget.28711

Correspondence to: Abhijit Basu — abhijit.basu@alumni.uni-ulm.de

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Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Protein GSK3β Offers New Angle on Overcoming Melanoma Drug Resistance

BUFFALO, NY - May 9, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on May 8, 2025, titled “METTL3 promotes oral squamous cell carcinoma by regulating miR-146a-5p/SMAD4 axis."

In this study, researchers Jayasree Peroth Jayaprakash, Pragati Karemore, and Piyush Khandelia from the Birla Institute of Technology and Science, India, discovered that a molecule called METTL3 contributes to the development and spread of oral squamous cell carcinoma (OSCC). The study shows that METTL3 increases the levels of a small RNA molecule called miR-146a-5p, which blocks SMAD4, a key tumor-suppressing gene. These findings help explain why oral cancers are difficult to treat and may offer a new target for more effective therapies.

Oral squamous cell carcinoma is a common and aggressive cancer affecting the mouth and throat. It has a high death rate, mainly due to late detection, treatment resistance, and the cancer’s ability to invade nearby tissues. In this study, the researchers focused on METTL3, an enzyme that adds chemical tags known as m6A marks to RNA, which change how genetic information is used by cells. They found that METTL3 is unusually active in OSCC cells, causing an increase in miR-146a-5p. This molecule, in turn, blocks the function of SMAD4, which helps control how cells grow and die in our bodies.

“METTL3, the primary m6A RNA methyltransferase, is significantly upregulated in OSCC cells leading to increased global m6A levels.”

When METTL3 was reduced or chemically blocked, miR-146a-5p levels dropped and SMAD4 levels increased. This shift slowed the growth of cancer cells, increased their death, and made them less likely to spread. When researchers reintroduced miR-146a-5p or lowered SMAD4 levels again, the cancer-promoting behavior returned. These results show that the METTL3–miR-146a-5p–SMAD4 pathway plays a key role in OSCC.

The findings open up new possibilities for treatment. Drugs that block METTL3 or miR-146a-5p or that restore SMAD4 could slow or stop tumor growth. One such drug, STM2457, which targets METTL3, has already shown promise in lab studies. As research progresses, targeting this molecular pathway may offer a new strategy in treating OSCC.

This discovery improves our understanding of how OSCC develops and avoids the body’s defenses. By interfering with this newly discovered pathway, future treatments may become more successful, improving survival rates and quality of life for people with this disease.

DOI - https://doi.org/10.18632/oncotarget.28717

Correspondence to - Piyush Khandelia - piyush.khandelia@hyderabad.bits-pilani.ac.in

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METTL3 Drives Oral Cancer by Blocking Tumor-Suppressing Gene

BUFFALO, NY - May 14, 2025 – A new #review paper was #published in Volume 16 of Oncotarget on May 9, 2025, titled “Relationship between ABO blood group antigens and Rh factor with breast cancer: A systematic review and meta-analysis."

A comprehensive study, led by first authors Rahaf Alchazal from Yarmouk University and Khaled J. Zaitoun from Johns Hopkins University School of Medicine and Jordan University of Science and Technology, examined the potential link between blood type and breast cancer. The research team conducted a systematic review and meta-analysis of 29 previously published studies, involving more than 13,000 breast cancer patients and over 717,000 controls. 

“Researchers searched for studies on breast cancer patients and ABO blood groups across four major databases: PubMed, Scopus, Web of Science, and Google.“

Breast cancer is the most common cancer among women worldwide. Identifying risk factors is vital for early detection and prevention. While many studies have explored lifestyle and genetic causes, this analysis focused on the ABO blood group system. By pooling global data, the researchers found that blood type A was the most common among breast cancer patients and was significantly associated with an 18% increased risk compared to type O.

The study did not find a significant association between breast cancer and blood types B, AB, or Rh factor. Although the results do not prove causation, they point to a biological pattern worth further investigation. Blood group antigens are proteins found on the surface of cells, including breast tissue. These molecules may influence how cancer develops and spreads by interacting with the immune system or affecting cell behavior.

This meta-analysis is the most extensive review to date on this topic, based on studies conducted across Asia, Europe, Africa, and the Americas. While previous research found unclear conclusions, this large-scale evaluation provides stronger evidence for a possible connection between blood type A and breast cancer risk.

Researchers note that regional differences, genetic diversity, and study quality may affect individual results. Nevertheless, the overall trend supports considering blood type A as a potential risk marker. This insight could help shape screening guidelines, encouraging earlier or more frequent checkups for women with this blood type.

Further research is needed to understand why blood type A may play a role in cancer development. Future studies may explore genetic mechanisms, immune responses, and other biological pathways. These efforts could lead the way for more personalized cancer prevention and care strategies.

DOI - https://doi.org/10.18632/oncotarget.28718

Correspondence to - Khaled J. Zaitoun - kzaitou1@jh.edu

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Keywords - cancer, breast cancer, cancer risk factors, blood group antigens, tumor

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Blood Type A Identified as Potential Breast Cancer Risk Factor

BUFFALO, NY – May 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 9, 2025, titled “Analytical validation of a circulating tumor DNA assay using PhasED-Seq technology for detecting residual disease in B-cell malignancies.”

In this study, a team from Foresight Diagnostics led by first author Nina Klimova and corresponding author Laura Hyland validated a new DNA-based blood test designed to detect minimal residual disease (MRD) in patients with B-cell cancers. This assay uses a highly sensitive method called Phased Variant Enrichment and Detection Sequencing (PhasED-Seq) to find tiny fragments of tumor DNA in the blood. Its ultra-sensitive detection capabilities offer a powerful tool for early cancer detection, monitoring treatment response, and predicting cancer reappearance.

B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL), are among the most prevalent blood cancers. Although many patients respond to initial treatment, up to 40% relapse. Standard monitoring methods such as imaging scans often miss low levels of cancer cells, creating a need for more precise tools. This study introduces a non-invasive blood test that improves the detection of MRD, a critical factor in guiding follow-up care and early intervention.

The test works by tracking unique groups of mutations known as phased variants in tumor DNA. These mutations are more specific to cancer and allow for highly accurate identification of tumor fragments in the bloodstream. The PhasED-Seq-based MRD assay was tested on three types of samples. First, blood plasma from healthy individuals was used to confirm the test does not give false positives. Second, researchers created controlled samples by mixing tumor DNA from lymphoma patients with healthy DNA to measure how sensitive and precise the test is. Finally, blood samples from patients with B-cell lymphoma were used to compare the new test to an existing method.

Across all sample types, the PhasED-Seq-based MRD assay demonstrated exceptional performance—capable of detecting fewer than one cancer DNA molecule per million normal DNA fragments. It also demonstrated a very low false positive rate and over 96% reproducibility across different laboratory conditions. Compared to an existing method, the new PhasED-Seq assay showed more than 90% agreement in positive results and nearly 78% agreement in negative results. In cases where the tests disagreed, the new method aligned more closely with actual clinical outcomes, including whether patients relapsed or stayed in remission.

“The background error rate of the PhasED-Seq-based MRD assay was 1.95E-08, or 1.95 mutant molecules in 100 million informative molecules.”

The findings support the use of PhasED-Seq-based MRD assays in routine clinical practice. It could be especially useful for identifying patients who need additional treatment even when imaging results appear normal. This aligns with updated clinical guidelines that encourage the use of blood-based DNA tests to supplement traditional scans in lymphoma care.

This study offers strong evidence that the PhasED-Seq-based MRD assay is a precise, reliable, and clinically relevant tool. By detecting signs of cancer earlier and more accurately, it may help clinicians tailor treatments to individual patients and improve long-term outcomes in B-cell malignancies.

DOI - https://doi.org/10.18632/oncotarget.28719

Correspondence to - Laura Hyland - laura.hyland@foresight-dx.com

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New Ultra-Sensitive DNA Blood Test for Detecting Residual Cancer in B-cell Lymphoma Patients

BUFFALO, NY - May 21, 2025 – A new #review was #published in Volume 16 of Oncotarget on May 19, 2025, titled “Advancements in bladder cancer treatment: The synergy of radiation and immunotherapy."

Researchers from the University of California, Irvine, led by Nazmul Hasan, reviewed recent clinical and scientific advances in combining radiation therapy with immunotherapy for bladder cancer. The article summarizes growing evidence that this combined approach may strengthen the immune response and improve long-term disease control. This strategy is especially important for patients who are not candidates for surgery or who respond poorly to conventional treatments.

Bladder cancer is a serious and frequent condition, particularly affecting older men. Traditional treatments—surgery, chemotherapy, and radiation—can be effective, but they often fail to prevent cancer reappearance in advanced cases. The review explores how combining radiation and immunotherapy could improve outcomes by helping the immune system detect and destroy cancer cells more effectively.

Radiation therapy destroys cancer cells and triggers the release of tumor signals that attract immune cells. Immunotherapy, including drugs like pembrolizumab and nivolumab, helps the immune system work better by blocking proteins that allow cancer to evade detection. Used together, these treatments may produce a stronger, more widespread anti-tumor effect, even at distant sites not directly targeted by radiation.

The review discusses several clinical trials that support this approach. One phase II study reported that combining radiation with the immunotherapy drug durvalumab led to promising survival rates and manageable side effects. Another trial in Australia tested pembrolizumab with radiation and chemotherapy, resulting in high tumor control and extended patient survival. However, the review also points out that other trials showed serious side effects when high doses or multiple immunotherapy drugs were used at once.

"Joshi et al. performed a phase II study to determine the safety and efficacy of combining radiation therapy with durvalumab, a PD-L1 inhibitor, in patients who were ineligible for surgery or cisplatin-based chemotherapy."

While the combination approach is promising, the authors emphasize that more research is needed to refine this treatment strategy. One major challenge is determining which patients are most likely to benefit. Future studies should focus on identifying reliable biomarkers, such as tumor mutation burden or immune activity, to guide personalized treatment plans.

This review highlights the potential of combining radiation and immunotherapy to improve outcomes for bladder cancer patients. With continued research and careful treatment design, this approach could offer new treatment options for those facing aggressive or hard-to-treat forms of the disease.

DOI - https://doi.org/10.18632/oncotarget.28723

Correspondence to - Nazmul Hasan - nhasan1@hs.uci.edu

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Keywords - cancer, bladder cancer, immunotherapy, radiation, microenvironment, abscopal

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Combining Radiation and Immunotherapy Shows Promise for Bladder Cancer

BUFFALO, NY – June 9, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 20, 2025, titled “Cigarette smoke and decreased DNA repair by Xeroderma Pigmentosum Group C use a double hit mechanism for epithelial cell lung carcinogenesis.”

In this study, led by first author Nawar Al Nasralla and corresponding author Catherine R. Sears, from the Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis and the Richard L. Roudebush Veterans Affairs Medical Center, researchers investigated how cigarette smoke and reduced DNA repair capacity contribute together to the development of lung cancer. They found that when a critical DNA repair protein called XPC is decreased and lung cells are exposed to cigarette smoke, the combination causes extensive damage and significantly increases cancer risk.

Non-small cell lung cancer (NSCLC) develops through both genetic and environmental factors. This study focused on how cigarette smoke affects the body’s natural ability to repair DNA. The researchers studied the role of XPC, a protein essential for recognizing and repairing harmful DNA changes caused by tobacco smoke. They found that low levels of XPC — commonly seen in lung cancer patients — made lung cells less capable of repairing DNA. This made the cells unstable and more likely to become cancerous. These changes were most pronounced in normal lung cells, suggesting that the earliest stages of disease occur before cancer is even detected.

The findings support a “double hit” model, where both cigarette smoke and reduced DNA repair work together to drive cancer development. In laboratory experiments, normal lung cells with low XPC levels showed more damage and cell death after cigarette smoke exposure. By contrast, lung cancer cells were more resistant to smoke damage, even when XPC was low, indicating that critical changes had likely occurred earlier in the disease process.

“Our study suggests that cigarette smoke exposure leads to decreased XPC mRNA expression, exacerbates total and oxidative DNA damage, hinders NER, and may contribute to lung cancer development.”

The study also showed that DNA repair ability declined significantly in healthy cells after smoke exposure, but this effect was not seen in cancer cells. In addition, the researchers confirmed that XPC gene activity was lower in actual lung tumor tissue compared to nearby healthy lung tissue. This pattern was consistent across both adenocarcinoma and squamous cell carcinoma, the two main types of NSCLC.

These results add to our understanding of how lung cancer begins at the molecular level. By showing how cigarette smoke and reduced DNA repair combine to create genetic instability, the research points toward new strategies for prevention. A better understanding of XPC’s role could help identify high-risk individuals and inform future efforts to stop lung cancer before it begins.

DOI - https://doi.org/10.18632/oncotarget.28724

Correspondence to - Catherine R. Sears - crufatto@iu.edu

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Keywords - cancer, DNA repair, DNA damage, lung adenocarcinoma, squamous cell carcinoma, Xeroderma Pigmentosum Group C (XPC)

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Cigarette Smoke and DNA Repair Deficiency Drive Lung Cancer Development

BUFFALO, NY - June 11, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 29, 2025, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib.”

A team led by first author Jinah Kim, from the University of Vermont Medical Center, and corresponding author Young Kwang Chae, from the Feinberg School of Medicine, reports a clinical case in which a patient with advanced non-small cell lung cancer (NSCLC) carrying rare EGFR mutations responded remarkably to amivantamab after other treatments had failed. The patient experienced a complete resolution of brain and spinal fluid metastases, suggesting that amivantamab may be a viable option for patients with uncommon genetic profiles and limited therapy options.

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Patients with NSCLC who have rare mutations in the EGFR gene often face limited treatment options and poor outcomes, especially when the disease spreads to the brain or spinal fluid. This case involved a 67-year-old man diagnosed with NSCLC who had two rare EGFR mutations—G719A and A289V. After disease progression on osimertinib and other therapies, the patient began amivantamab monotherapy.

Within six weeks, his lung tumor shrank by over 30 percent. By six months, imaging confirmed the disappearance of brain metastases and leptomeningeal disease, a serious condition affecting the membranes of the brain and spinal cord. Blood tests showed no detectable cancer-related mutations, and the patient, previously wheelchair-bound, regained the ability to walk and perform daily activities. This response has been sustained for more than 19 months.

 “Treatment produced a durable response over 19 months, including a 32.2% reduction in tumor size at six weeks, and complete resolution of brain metastases and LMD by six months.”

Amivantamab is a bispecific antibody that targets EGFR and MET, two key drivers of tumor growth. While it is approved in combination regimens for common EGFR mutations, its effectiveness as a single agent in rare mutations or in treating brain metastases remains largely unproven. This case challenges the assumption that large antibody drugs cannot cross the blood-brain barrier and suggests that amivantamab may have potential in managing central nervous system involvement. Further research is needed to clarify how the drug achieves these effects and to explore its broader use in patients with rare EGFR mutations and limited treatment options.

This case highlights three key findings: amivantamab may be effective against rare EGFR mutations, can be used as monotherapy, and may overcome the challenges of the blood-brain barrier. Although based on a single patient, the results provide encouraging evidence to support further investigation of amivantamab in treating difficult-to-manage forms of NSCLC.

DOI - https://doi.org/10.18632/oncotarget.28730

Correspondence to - Young Kwang Chae - young.chae@northwestern.edu

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Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal disease

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Rare Non-Small Cell Lung Cancer with Brain Metastases Responds to Amivantamab Monotherapy

BUFFALO, NY - June 17, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 10, 2025, titled “Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence.”

The study, led by first author Kavin Sugumar and corresponding author Jordan M. Winter, from University Hospitals Seidman Cancer Center, reports on a rare group of pancreatic cancer (PC) patients who responded remarkably well to immunotherapy, a treatment typically considered ineffective for this cancer type. The analysis, which includes data from 14 patients across multiple U.S. institutions, identifies outcomes that could help refine treatment strategies for one of the most aggressive and deadly forms of cancer.

“Between 2020–21, 471 oncologists from 91 major cancer centers in the United States were contacted.”

Pancreatic cancer has among the lowest survival rates and few effective therapies. While immunotherapy has transformed the treatment landscape for several other cancers, it generally offers little benefit for pancreatic cancer. However, this study highlights a small but important group of patients who experienced significant and sustained responses to immune-based treatment without chemotherapy. Most had advanced or metastatic disease and had already progressed after standard treatments.

Among the 14 patients, 82% had partial tumor shrinkage, and nearly one-third had a notable decrease in tumor markers. The median progression-free survival was 12 months, and most patients were still alive at follow-up, with survival rates of 80% at one year and 70% at two years. These outcomes contrast sharply with standard therapies, which often provide only a few months of benefit for similar patients.

Interestingly, while some patients had high microsatellite instability (MSI-high)—a known marker for immunotherapy success—more than half did not, suggesting other biological mechanisms may be involved. This result highlights the need for new biomarkers to be discovered to predict treatment response in future studies.

This case series is the largest focused exclusively on exceptional immunotherapy responders in pancreatic cancer. By excluding patients who received chemotherapy, the study isolates the effects of immune-based drugs, including PD-1 inhibitors such as pembrolizumab and nivolumab, CTLA-4 inhibitors like ipilimumab, and agents targeting macrophages.

While the sample size is small, the findings challenge the assumption that immunotherapy is ineffective for nearly all pancreatic cancer patients. The study suggests that, under certain biological conditions, this treatment can be remarkably successful. Further research is needed to understand the underlying mechanisms.

This work supports the need to reconsider how clinical trials are designed for pancreatic cancer and who is eligible for immunotherapy. Broader criteria and more personalized molecular profiling could help uncover hidden opportunities for treatment in this highly lethal cancer.

DOI - https://doi.org/10.18632/oncotarget.28739

Correspondence to - Jordan M. Winter - jordan.winter@UHHospitals.org

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Rare Pancreatic Cancer Patients Show Strong Response to Immunotherapy

BUFFALO, NY – June 20, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 10, 2025, titled “Beyond DNA damage response: Immunomodulatory attributes of CHEK2 in solid tumors.”

In this paper, led by first author Helen Qian and corresponding author Crismita Dmello from Northwestern University Feinberg School of Medicine, researchers compiled growing evidence that the CHEK2 gene, long known for its role in repairing DNA damage, may also influence how tumors respond to immunotherapy. Their analysis suggests that problems in CHEK2 function might make cancer cells more vulnerable to immune system attacks, highlighting a new opportunity to improve treatment outcomes in solid tumors.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment; however, they are effective in only a subset of patients. This review suggests that tumors with reduced CHEK2 activity may accumulate more mutations that produce signals the immune system can recognize. These signals, known as neoantigens, help immune cells identify and destroy cancer cells more effectively. The review connects this process not only to CHEK2’s established role in the DNA damage response but also to a newly proposed function in shaping the immune environment of tumors.

CHEK2 normally helps maintain genomic stability by enabling precise DNA repair. When this function is lost, cells rely on more error-prone repair methods, leading to additional mutations. These mutations can increase tumor mutational burden, which has been linked to better outcomes with immunotherapy. Beyond DNA repair, the review highlights a second mechanism: activation of the cGAS-STING pathway. This pathway detects fragments of damaged DNA and triggers inflammation that attracts immune cells to the tumor.

The authors highlight studies where CHEK2-deficient tumors responded better to PD-1 inhibitors, a common type of immune checkpoint inhibitor. In both lab models and early-stage clinical settings, CHEK2 loss was associated with increased infiltration of CD8+ T cells—immune cells essential for attacking cancer cells. In cancers such as glioblastoma and renal cell carcinoma, which are typically resistant to immunotherapy, reduced CHEK2 expression was linked with more favorable immune activity and higher expression of interferon-related genes.

The compiled evidence points to CHEK2 as a potential biomarker for identifying patients likely to respond to immunotherapy. In addition, combining CHEK2 inhibitors with existing immunotherapies may enhance anti-tumor effects, particularly in cancers with limited treatment options. The review notes that some clinical trials using the CHEK1/2 inhibitor prexasertib alongside immune checkpoint therapies have already shown promising early results.

“The initial results from this Phase I clinical trial support the immunomodulatory role of CHEK2 expression and even suggest CHEK2 potentiates immunosuppression.”

Although more research is needed to confirm these mechanisms and improve treatment approaches, this review underscores the expanding role of DNA repair genes like CHEK2—not only in maintaining genome integrity but also in helping the immune system fight cancer.

DOI - https://doi.org/10.18632/oncotarget.28740

Correspondence to - Crismita Dmello - stellacpak@outlook.com

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CHEK2 Identified as a Potential Target to Improve Immunotherapy in Solid Tumors

BUFFALO, NY – July 1, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Optimizing enfortumab vedotin plus pembrolizumab therapy.”

First authors Elias Antoine Karam of the Gustave Roussy and Saint-Joseph University of Beirut and Yaghi César Céline from  the Saint-Joseph University of Beirut, along with their colleagues, reviewed recent developments about treating advanced urothelial carcinoma (aUC), an aggressive form of bladder cancer. Their review highlights how combining enfortumab vedotin and pembrolizumab as a first-line treatment offers a major improvement for patients with limited options and poor prognoses.

Advanced urothelial cancer has traditionally been treated with platinum-based chemotherapy, which often causes serious side effects and offers limited long-term benefit. Many patients are even ineligible for it due to underlying health conditions. The new combination presents a more effective and better-tolerated alternative, as shown in recent clinical trials reviewed by the authors.

Enfortumab vedotin targets Nectin-4, a protein present in most urothelial cancer cells, delivering a cancer-killing agent directly into tumors. Pembrolizumab helps the immune system detect and destroy cancer cells. Together, they have shown strong results in extending survival with fewer serious side effects than chemotherapy. These findings led to FDA approval in 2023 for use in a broad range of patients, including those unable to tolerate traditional treatments.

“In the phase II KEYNOTE-052 study, pembrolizumab demonstrated significant efficacy as initial therapy in patients with aUC who were ineligible for a cisplatin-based regimen.”

The review also compares this new approach with other evolving strategies, such as therapies using nivolumab and chemotherapy combinations. Among current first-line options, enfortumab vedotin and pembrolizumab have produced the most promising outcomes. However, the best course of action following disease progression remains unclear.

Other important challenges raised in the review include the high cost of the new therapies, limited patient access to them, and the absence of reliable biomarkers to predict individual response. The authors call for further studies to refine treatment strategies and explore blood-based tools that could guide therapy decisions and minimize side effects.

This review offers a clear summary of how recent clinical advances are reshaping the treatment of aUC. It reflects a shift away from traditional chemotherapy toward immunotherapy and targeted, personalized treatments that aim to extend survival and improve quality of life.

DOI - https://doi.org/10.18632/oncotarget.28741

Correspondence to - Elias Antoine Karam - eliaskaram18@gmail.com

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Keywords - cancer, advanced urothelial carcinoma (aUC), enfortumab vedotin, pembrolizumab, treatment strategies, bladder cancer

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New Drug Combination Redefines First-Line Treatment for Advanced Urothelial Cancer

BUFFALO, NY - July 7, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience.”

In this study, a research team led by first author Fei Fei and corresponding author Michelle Afkhami from the City of Hope Comprehensive Cancer Center investigated a rare and aggressive type of blood cancer called blastic plasmacytoid dendritic cell neoplasm (BPDCN). Their research uncovered frequent mutations in key genes and identified CCDC50 as a potential biomarker for diagnosis and disease monitoring. These findings could help improve how this cancer is detected and treated in the future.

BPDCN most often affects older adults and is known for its rapid progression and poor survival rates. The researchers performed genetic sequencing on 21 patients to better understand the disease. They found that two genes, TET2 and ASXL1, were frequently mutated in these patients and were linked to worse survival, especially in those over 65 years old.

“Our study revealed that TET2 (57%) and ASXL1 (33%) were the most frequently mutated genes, followed by NRAS (29%), SRSF2 (14%), ZRSR2 (14%), and KMT2D (14%).”

The study also discovered that a gene called CCDC50 was expressed at much higher levels in BPDCN samples compared to other blood cancers, such as acute myeloid leukemia and chronic monomyelocytic leukemia. This suggests that CCDC50 may help clinicians distinguish BPDCN from other similar diseases. Importantly, CCDC50 levels dropped significantly in patients whose disease went into remission, highlighting its potential as a tool for tracking disease activity over time.

Researchers further observed that patients who received stem cell transplants lived longer than those who did not, reinforcing the importance of this treatment approach. However, BPDCN remains a challenging disease with an overall poor outlook, making these findings an important step toward better care.

This research provides new insights into the genetic changes behind BPDCN and points to CCDC50 as a promising marker to improve diagnosis and monitor treatment success. Larger studies will be needed to confirm these results and bring these discoveries closer to use in routine medical practice.

DOI - https://doi.org/10.18632/oncotarget.28742

Correspondence to - Michelle Afkhami - mafkhami@coh.org

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Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50

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Key Genetic Alterations and Biomarker for Blastic Plasmacytoid Dendritic Cell Neoplasm

BUFFALO, NY – July 14, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 25, 2025, titled “Hypoxia induced lipid droplet accumulation promotes resistance to ferroptosis in prostate cancer.”

In this study, researchers led by Shailender S. Chauhan and Noel A. Warfel from the University of Arizona discovered that prostate cancer cells survive treatment by storing fats in tiny cellular compartments when oxygen levels are low. This process makes the cancer cells less vulnerable to a type of cell death known as ferroptosis. The findings provide new insight into why prostate tumors often resist therapies and suggest potential strategies to improve treatment outcomes.

This study focused on ferroptosis, a form of programmed cell death that relies on iron and lipid oxidation to destroy cancer cells. Researchers tested prostate cancer cells under normal and low oxygen conditions and found that hypoxia, or reduced oxygen levels, allowed cancer cells to build up lipid droplets (LD). These structures act as storage units for fats, shielding cancer cells from oxidative damage and preventing ferroptosis from occurring.

The researchers found that this adaptation of prostate cancer cells made them less sensitive to ferroptosis-inducing drugs like Erastin and RSL3, even when these drugs were combined for a stronger effect. The team also reported that hypoxia caused significant changes in lipid metabolism, decreasing the availability of specific fatty acids that normally promote ferroptosis. 

“Transcriptomic analysis revealed that hypoxia significantly reduced the expression of genes related to incorporating polyunsaturated fatty acids into phospholipids (ACSL4, LPCAT3), and parallel lipidomic analysis demonstrated that hypoxia significantly decreased the levels of the ferroptosis-prone lipid class, phosphatidylethanolamine (PE) and increased production of neutral lipid species, cholesteryl ester (ChE (22:5)) and triglycerides (TG(48:1), TG:(50:4), and TG(58:4)).”

This research highlights the importance of the tumor microenvironment, particularly oxygen levels, in shaping how cancer cells respond to therapy. By altering their metabolism and storing lipids, prostate tumors may evade treatments designed to trigger ferroptosis. These findings underscore the need to develop new strategies targeting LD dynamics or lipid metabolism to overcome this resistance.

Understanding how prostate cancer (Pca) adapts to survive in hypoxic conditions offers a potential avenue for improving therapies. For example, preventing lipid accumulation in cancer cells or releasing stored fats may restore their sensitivity to ferroptosis and improve the effectiveness of current therapies. This approach could have broader implications for treating other solid tumors that share similar metabolic features.

DOI - https://doi.org/10.18632/oncotarget.28750

Correspondence to - Noel A. Warfel - warfelna@arizona.edu, and Shailender S. Chauhan - shailenderc@arizona.edu

Video short - https://www.youtube.com/watch?v=xFypDT4ALmc

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Keywords - cancer, hypoxia, lipid droplets, ferroptosis, resistance, prostate

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Prostate Cancer Cells Survive Treatment by Storing Fat in Low Oxygen Conditions

BUFFALO, NY - July 16, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 9, 2025, titled “A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment.”

In this study, researchers from the National Institute of Allergy and Infectious Diseases, led by first author Maja Buszko and corresponding author Ethan M. Shevach, discovered a new monoclonal antibody that selectively targets a subset of immune cells called regulatory T cells (Tregs). These cells, while normally important for preventing autoimmunity, also can block the body’s ability to fight cancer by suppressing anti-tumor immune responses. This discovery could lead to novel cancer therapies that strengthen the immune system’s capacity to attack tumors.

The researchers identified an anti-CD25 monoclonal antibody with several atypical properties and named it 2B010.  To evaluate its effects, they used humanized mice, laboratory mice that are engineered to carry human immune cells, to closely mimic how human immune systems respond to cancer. The treatment of these mouse models with 2B010 significantly decreased the number of Tregs in tumors and boosted the activity of CD8+ T cells, which are essential for killing cancer cells. Importantly, 2B010 worked without disrupting other key immune functions. Unlike traditional Anti-CD25 antibodies, it did not interfere with interleukin-2 (IL-2) signaling, which is essential for the growth and activity of effector T cells that fight cancer. 

“2B010 also had no effect on IL-2 induced STAT5 phosphorylation or CD4+ T cell proliferation in vitro while both were blocked by Clone D1 further supporting the view that 2B010 does not recognize the IL-2 binding site.”

This finding is especially significant because high levels of Tregs in tumors are associated with poor outcomes in many cancers. By specifically removing these cells, 2B010 may help overcome one of the main barriers to current immunotherapy approaches. Its ability to preserve IL-2 signaling could also make it safer and more effective when used alone or in combination with existing therapies such as immune checkpoint inhibitors.

While the 2B010 antibody showed strong effects in reducing Tregs and boosting immune cell activity, the study did not observe changes in tumor size in these models. Researchers suggest this may be due to limitations in the preclinical systems used, such as the lack of tumor-specific T cells in humanized mice. Nevertheless, these findings demonstrate that 2B010 has a unique mechanism of action that could complement other cancer immunotherapies in future clinical trials.

In conclusion, the development of 2B010 is a promising step toward selectively disrupting the immune suppressive environment in tumors. As researchers continue to refine and test this antibody, it could become a powerful tool for enhancing the effectiveness of cancer treatments and improving outcomes for patients.

DOI - https://doi.org/10.18632/oncotarget.28752

Correspondence to - Ethan M. Shevach - eshevach@Niaid.NIH.gov

Video short - https://www.youtube.com/watch?v=2NJcGsI7WXA

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Keywords - cancer, Treg, CD25, TME, mAb, GVHD

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New Antibody Selectively Targets Immune Cells That Suppress Anti-Tumor Responses

BUFFALO, NY - July 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 25, 2025, titled “Comprehensive genomic profiling of over 10,000 advanced solid tumors.”

In this study, led by Jean-Paul De La O from Exact Sciences Corporation, researchers analyzed data from over 10,000 solid tumor samples from patients with advanced cancer and found that more than 90 percent contained genetic changes that could guide treatment. This work demonstrates the growing impact of large-scale tumor DNA and RNA testing on patient care.

The researchers retrospectively analyzed OncoExTra assay information for 31 types of cancer, including breast, colorectal, prostate, lung, and ovarian cancers. Their analysis revealed that nearly a third of patients had alterations associated with approved drugs for their specific cancer, while another third had changes linked to therapies approved for other cancers. These results show that detailed genetic profiling could expand treatment choices.

“Biomarkers associated with on- or off-label FDA-approved therapies were detected in 29.2% and 28.0% of samples, respectively.”

Another relevant discovery was that many important mutations occurred at very low levels, which are often missed by simpler tests. By using a broad and highly sensitive approach, the scientists were able to identify these rare mutations. They also reported that 7.5 percent of samples carried gene fusions, unusual genetic events that can drive cancer growth. Such findings can be critical in selecting therapies that specifically target these abnormalities.

The study also highlighted the value of RNA sequencing in detecting fusion events that traditional DNA tests might miss. Prostate cancer and certain sarcomas showed particularly high rates of these fusion alterations. This type of information can refine cancer diagnosis and improve therapy planning.

In addition, the researchers identified changes in several major cancer-related pathways, including those that control cell growth, DNA repair, and immune system response. Alterations in these pathways can point to newer treatment options, such as immunotherapy or drugs designed to block specific cell signals.

Overall, this study shows that comprehensive genomic profiling can guide more personalized cancer care by identifying mutations, gene fusions, and other molecular patterns. Advanced testing methods like the OncoExTra assay reveal treatment opportunities even in advanced cancers, ensuring that subtle but important genetic changes are detected.

DOI - https://doi.org/10.18632/oncotarget.28757

Correspondence to - Jean-Paul De La O - jdelao@exactsciences.com

Video short - https://www.youtube.com/watch?v=awiRhDfiMTE

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Keywords - cancer, solid tumors, comprehensive genomic profiling, matched therapy, gene fusions, limit of detection

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Comprehensive Genomic Testing Reveals Treatment Targets in 90% of Advanced Solid Tumors

BUFFALO, NY – August 15, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 13, 2025, titled “Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.”

In this study, first authors Valeriy Domenyuk and Kasey Benson, along with corresponding author David Spetzler from Caris Life Sciences in Irving, Texas, introduce MI Cancer Seek, an FDA-approved test designed to deliver comprehensive tumor profiling. MI Cancer Seek demonstrated strong concordance with other FDA-approved companion diagnostics and serves as a powerful tool to guide treatment decisions in both adult and pediatric cancer patients.

Cancer remains one of the most complex and diverse diseases to treat. With many targeted therapies currently FDA-approved, selecting the right one for a specific patient requires detailed genetic insights. MI Cancer Seek addresses this need by analyzing both DNA and RNA from a single tumor sample. The tool identifies key biomarkers linked to FDA-approved treatments for several major cancers, including breast, lung, colon, melanoma, and endometrial cancers.

One of the most significant strengths of MI Cancer Seek is its ability to deliver accurate and reliable results from minimal tissue input (50 ng). Even when analyzing formalin-fixed paraffin-embedded samples, which are widely used but often degraded, the test maintained high levels of accuracy. It successfully detected important genetic alterations such as PIK3CA, EGFR, BRAF, and KRAS/NRAS mutations and measured tumor mutational burden (TMB) and microsatellite instability (MSI), both of which are key indicators for immunotherapy response.

In clinical comparisons, the test achieved over 97% agreement with other FDA-approved diagnostic tools, confirming its reliability in detecting critical biomarkers. Notably, it showed near-perfect accuracy in identifying MSI status in colorectal and endometrial cancers. The researchers also demonstrated that the test maintains precision across different lab conditions and varying DNA input levels, confirming its robustness for routine clinical use.

Beyond its role as a companion diagnostic, MI Cancer Seek incorporates additional features developed under its predecessor, MI Tumor Seek Hybrid. These include detection of homologous recombination deficiency, structural variants, and cancer-related viruses. It also includes advanced tools such as the Genomic Probability Score for identifying the tissue of origin in cancers of unknown primary, as well as a gene signature to guide first-line chemotherapy in colorectal cancer.

“One limitation to be considered is the low PPA for ERBB2 CNA detection.”

By offering deeper genetic insights from a single, small sample, MI Cancer Seek has the potential to streamline diagnostics, reduce testing costs, and connect patients to effective therapies more quickly. As precision medicine continues to expand, this assay stands out as a comprehensive and efficient solution for meeting the evolving needs of modern oncology.

DOI - https://doi.org/10.18632/oncotarget.28761

Correspondence to - David Spetzler - dspetzler@carisls.com

Video short - https://www.youtube.com/watch?v=D4hd2FxCYY8

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FDA-Approved MI Cancer Seek Test Enhances Tumor Profiling for Precision Oncology

BUFFALO, NY – August 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 29, 2025, titled “In vivo manipulation of the protein homeostasis network in rhabdomyosarcoma.”

In this study led by first author Kristen Kwong and corresponding author Amit J. Sabnis from the Department of Pediatrics, Division of Oncology, University of California San Francisco, researchers discovered that disrupting the protein quality control system in cancer cells slows tumor growth in rhabdomyosarcoma (RMS), the most common pediatric soft tissue cancer. This finding points to a new strategy for treating high-risk childhood cancers that often resist current therapies.

Rhabdomyosarcoma is a rare and aggressive cancer that primarily affects children and adolescents. Standard treatments like chemotherapy and radiation often have limited long-term success in high-risk cases. This study explored a different approach: targeting the cellular machinery that maintains protein quality, known as the proteostasis network. Cancer cells rely heavily on this system to survive stress caused by rapid growth and genetic instability.

“To examine whether MAL3-101 or more drug-like proteostasis inhibitors represent a new therapeutic strategy for RMS, we screened proteostasis components that might recapitulate the effects of MAL3-101 in vivo.”

The researchers first used a compound called MAL3-101 to disrupt protein control in RMS cells. They then identified which parts of the protein quality system were affected. Based on those findings, they searched for more drug-like compounds that could target the same pathways. 

They focused on a protein called p97, which plays a critical role in removing damaged or misfolded proteins. When they blocked p97 using a drug called CB-5083, the cancer cells could no longer manage internal stress and began to self-destruct. In both laboratory models and mice implanted with human RMS tumors, the treatment significantly slowed or stopped tumor growth. The drug triggered a stress response in the cells known as the unfolded protein response, which can lead to either recovery or programmed cell death.

However, not all tumors responded the same way. Some resisted the treatment by activating a backup system called autophagy, which allows cells to recycle parts of themselves under stress. By comparing tumors that responded well to those that did not, the researchers found that higher autophagy activity could serve as a warning sign for resistance. This insight may help identify which patients are more likely to benefit from therapies that target protein quality control.

While the results are promising, the drug’s effectiveness depended on the tumor’s genetic profile and how it handled stress. Combining p97 inhibition with other treatments or blocking alternative survival pathways like autophagy may improve outcomes. The researchers also noted the importance of developing safer and more targeted drugs to reduce side effects.

This study opens new possibilities for personalized cancer treatment, particularly for children with aggressive or relapsed RMS. By weakening the systems that cancer cells depend on to survive, rather than only using toxic treatments to kill them, scientists aim to develop more effective and less harmful therapies for young patients.

DOI - https://doi.org/10.18632/oncotarget.28764

Correspondence to - Amit J. Sabnis - amit.sabnis@ucsf.edu

Video short - https://www.youtube.com/watch?v=YsdffTkXNRQ

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Blocking Protein Control Pathway Slows Rhabdomyosarcoma Growth in Mice

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Although precision medicine has improved outcomes for many patients, certain rare genetic mutations are still poorly understood, particularly in regions with limited access to genomic testing. Such mutations involve the HER2 gene, better known for its role in breast cancer but also implicated in a small subset of lung cancers.

HER2 mutations are found in approximately 2–4% of non-small cell lung cancer (NSCLC) cases and create unique challenges. These tumors can vary significantly in how they appear under a microscope and in how they respond to treatment. Adding to the complexity, most diagnostic and treatment guidelines are based on research from high-income countries, which may not reflect the genetic diversity seen in other parts of the world.

To help close this knowledge gap, researchers in Northeastern Brazil conducted one of the first detailed investigations into HER2-mutated NSCLC in Latin America. Their study, recently published in Volume 16 of Oncotarget, reveals a complex and often overlooked form of the disease, highlighting the need for broader access to targeted therapies in underserved populations.

Full blog - https://www.oncotarget.org/2025/10/08/new-insights-into-her2-mutated-non-small-cell-lung-cancer-in-brazil/

Paper DOI - https://doi.org/10.18632/oncotarget.28737

Correspondence to - Fabio Tavora - stellacpak@outlook.com

Abstract video - https://www.youtube.com/watch?v=hr5R9iDBFFI

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Keywords - cancer, HER2 mutation, NSCLC, lung cancer, targeted therapy, genomic profiling

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New Insights into HER2-Mutated Non-Small Cell Lung Cancer in Brazil

BUFFALO, NY – October 14, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 13, 2025, titled “Treatment of glioblastoma with tumor-specific amplitude-modulated radiofrequency electromagnetic fields.”

The study, led by Hugo Jimenez from Wayne State University School of Medicine, Karmanos Cancer Institute, introduces a novel treatment approach for glioblastoma, an aggressive and often treatment-resistant brain cancer. The findings open a new potential path for patients who currently have limited therapeutic options.

The approach uses a device developed by TheraBionic that delivers extremely low levels of radiofrequency electromagnetic fields, tuned to frequencies associated with glioblastoma. In laboratory experiments, this therapy significantly slowed the growth of multiple glioblastoma cell lines. It was especially effective against tumor stem cells, which are known to resist standard treatments and drive cancer reappearance. Researchers also found that the treatment’s effects depend on a calcium channel in tumor cells known as Cav3.2 (CACNA1H). When this channel was blocked, the therapy lost its effectiveness, highlighting the channel’s essential role in how tumor cells respond to the signal. 

The therapy also disrupted the process of cell division by interfering with the mitotic spindle, a structure critical for cell replication. This disruption was associated with changes in the expression of genes that regulate cell division, particularly those involved in the “Mitotic Roles of Polo-Like Kinase” pathway. These effects were specific to tumor-targeted frequencies, as non-matching signals had no measurable impact.

The study also includes data from two patients with difficult-to-treat brain tumors who received the therapy through compassionate use. One patient with recurrent glioblastoma showed signs of clinical and radiographic improvement after one month of treatment. Another patient with oligodendroglioma tolerated the therapy well and had stable disease during follow-up imaging. Neither patient experienced serious side effects, further supporting the safety of the therapy.

“There was evidence of clinical and radiological benefit in a 38-year-old patient with recurrent GB and evidence of safety and feasibility in a 47-year-old patient with oligodendroglioma.”

This is the first study to demonstrate that tumor-specific radiofrequency therapy can suppress both tumor growth and cancer stem cells in glioblastoma. Similar results had previously been observed in liver and breast cancers. These findings contribute to the growing body of evidence supporting a new class of systemic, non-toxic cancer therapies. Further clinical trials will be crucial to confirm these results and fully assess the potential of this approach for treating brain cancer.

DOI - https://doi.org/10.18632/oncotarget.28770

Correspondence to - Hugo Jimenez - hugo.jimenez@wayne.edu

Abstract video - https://www.youtube.com/watch?v=uxYnWcNKYfg

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Keywords - cancer, oncology, amplitude-modulated radiofrequency electromagnetic fields, glioblastoma, TheraBionic, CACNA1H, Cav3.2

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New Radiofrequency Therapy Slows Glioblastoma Growth and Targets Tumor Stem Cells

BUFFALO, NY – October 20, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 16, 2025, titled “Widespread folate receptor expression in pediatric and adolescent solid tumors – opportunity for intraoperative visualization with the novel fluorescent agent pafolacianine.”

In this study, led by first author Ashley C. Dodd from Ann & Robert H. Lurie Children’s Hospital and corresponding author Timothy B. Lautz from the same institution and Northwestern University Feinberg School of Medicine, researchers discovered that folate receptor beta (FRβ) is widely expressed in various pediatric and adolescent solid tumors. This finding highlights FRβ as a promising target for improving the accuracy of tumor surgery using a fluorescent imaging agent known as pafolacianine.

Pediatric cancers are often challenging to remove completely during surgery, particularly when tumors spread or form small metastases. Fluorescence-guided surgery is a method that helps surgeons better identify tumors during operations using special imaging dyes. However, commonly used dyes such as indocyanine green are not tumor-specific and rely on general features of blood vessel permeability, limiting their precision.

In this study, researchers investigated the potential of pafolacianine, a next-generation dye that targets folate receptors, for pediatric use. Folate receptors are proteins commonly found on the surface of cancer cells. Pafolacianine is already FDA-approved for adults with ovarian and lung cancers due to its ability to bind these receptors and highlight tumors during surgery. 

The research team analyzed tissue samples from 13 young patients diagnosed with various cancers, including Wilms tumor, osteosarcoma, synovial sarcoma, rhabdomyosarcoma, Ewing sarcoma, and neuroblastoma. The results showed that FRα was predominantly absent, whereas FRβ was present in 100% of the tumor samples. Notably, FRβ appeared both on the tumor cells and in the surrounding tumor microenvironment but showed little to no expression in normal tissue, making it an excellent candidate for targeted imaging.

“In this study, we performed immunohistochemistry staining on slides obtained from a range of pediatric patients with solid tumors.”

This consistent expression of FRβ in pediatric tumors is a significant and novel finding. Earlier studies primarily linked FRβ to immune cells called tumor-associated macrophages. This study reveals that FRβ is also expressed directly on tumor tissue, which could help surgeons better distinguish cancer from healthy tissue during procedures.

Based on these results, the team has launched a clinical trial to evaluate pafolacianine in children undergoing surgery for metastatic lung tumors. If successful, this method could make pediatric cancer surgery safer and more effective.

Overall, this study suggests that targeting FRβ with pafolacianine could serve as a tumor-agnostic imaging strategy, applicable across a wide range of pediatric solid tumors. This represents a potential advancement in real-time surgical imaging and a step forward in pediatric cancer care.

DOI - https://doi.org/10.18632/oncotarget.28772

Correspondence to - Timothy B. Lautz - TLautz@luriechildrens.org

Abstract video - https://www.youtube.com/watch?v=0its0QkOcwM

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Folate Receptor Beta Found in Pediatric Tumors May Improve Fluorescence-Guided Cancer Surgery

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare blood cancer that primarily affects older adults. One of the key challenges in diagnosing and treating BPDCN is that it closely resembles other forms of leukemia in both appearance and behavior. This overlap often leads to delays or uncertainty in diagnosis, especially since currently there is no single, reliable marker that clearly distinguishes BPDCN from related diseases.

To address this issue, researchers from the City of Hope Comprehensive Cancer Center investigated the genetic profile of BPDCN.  Their study, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience,” was published in Oncotarget (Volume 16).

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Paper DOI - https://doi.org/10.18632/oncotarget.28742

Correspondence to - Michelle Afkhami - mafkhami@coh.org

Abstract video - https://www.youtube.com/watch?v=wUjr3uU3onI

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Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50

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Genetic Study Identifies Potential Diagnostic Marker for Rare Blood Cancer BPDCN

Prostate cancer is one of the most common cancers in men. While treatment options have improved, advanced stages of the disease remain difficult to manage. One promising approach involves a process called ferroptosis. This is a type of programmed cell death that relies on iron and lipid oxidation to kill cancer cells by damaging specific fats in their outer membrane. These fats are especially vulnerable in environments with normal oxygen levels.

However, many prostate tumors grow in low-oxygen areas of the body, a condition known as hypoxia, where ferroptosis becomes less effective. A recent study, titled “Hypoxia induced lipid droplet accumulation promotes resistance to ferroptosis in prostate cancer,” and published on Oncotarget (Volume 16), explores how oxygen-poor environments help prostate cancer cells resist treatment and what strategies could help overcome this resistance.

Full blog - https://www.oncotarget.org/2025/11/06/how-low-oxygen-shields-prostate-cancer-from-ferroptosis-therapies/

Paper DOI - https://doi.org/10.18632/oncotarget.28750

Correspondence to - Noel A. Warfel - warfelna@arizona.edu, and Shailender S. Chauhan - shailenderc@arizona.edu

Abstract video - https://www.youtube.com/watch?v=xFypDT4ALmc

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Keywords - cancer, hypoxia, lipid droplets, ferroptosis, resistance, prostate

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How Low Oxygen Shields Prostate Cancer from Ferroptosis Therapies

BUFFALO, NY - November 10, 2025 – A new #research paper was #published in Oncotarget (Volume 16) on November 6, 2025, titled “Anti-DNA virus agent cidofovir - loaded green synthesized cerium oxide nanoparticles (Nanoceria): Nucleic acids (DNA and RNA) binding affinity and cytotoxicity effects.”

In this study, led by Nahid Shahabadi from Razi University in Kermanshah, researchers developed an environmentally friendly approach to enhance the performance of cidofovir, a drug used to treat infections caused by DNA viruses. The work responds to the growing need for therapies that are safer, more effective, and better targeted.

The research team developed a new compound by loading cidofovir onto green-synthesized cerium oxide nanoparticles (nanoceria), known as CDV-CeO2 NPs. This method combines the drug’s antiviral and anticancer properties with the biological activity of nanoceria, which is known for its antioxidant, anti-inflammatory, and tumor-targeting effects. To avoid toxic chemicals, the nanoparticles were synthesized using quince fruit peel extract, making the process more sustainable and suitable for medical applications.

Laboratory experiments showed that the CDV-CeO2 nanoparticles were significantly more effective at killing breast cancer cells than either cidofovir or cerium oxide nanoparticles alone. At the highest tested concentration, the new compound destroyed more than 97% of cancer cells, compared to 72% with cidofovir alone and 50% with nanoparticles alone. These findings suggest that the combined formulation enhances anticancer activity and may allow for lower drug doses with fewer side effects.

To understand how these nanoparticles interact with genetic material, the team studied their binding to DNA and RNA, two key molecules involved in cancer development and viral replication. CDV-CeO2 nanoparticles showed strong binding affinity through two mechanisms: groove binding, which fits into natural curves of the genetic molecule strands, and intercalation, which inserts between base pairs. The nanoparticles formed stable complexes that responded to temperature, indicating reliable interactions in biological systems.

“The novelty of this work lies in the innovative green synthesis method, the dual-functional therapeutic application, and the enhanced biological activity of the CDV-CeO2 NPs, which collectively position these nanoparticles as promising candidates for future cancer and antiviral therapies.”

This research presents a potential new strategy for improving drug targeting and delivery using green nanotechnology. The approach could lead to more effective treatments for diseases such as breast cancer and infections caused by human papillomavirus (HPV) and other DNA viruses. However, further research, including animal and clinical studies, is needed to confirm the safety and long-term effectiveness of this treatment.

Overall, this study represents a significant step toward combining natural materials with nanomedicine to create more efficient therapies. If supported by future research, CDV-CeO2 nanoparticles could offer a new generation of dual-action treatments.

DOI - https://doi.org/10.18632/oncotarget.28774

Correspondence to - Nahid Shahabadi - nahidshahabadi@yahoo.com

Abstract video - https://www.youtube.com/watch?v=Il9CsfgO2mU

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Eco-Friendly Nanoparticles Improve Cidofovir’s Anticancer and Antiviral Effects

BUFFALO, NY - November 12, 2025 – A new #research paper was #published in Oncotarget (Volume 16) on November 6, 2025, titled “LRIG1-3 in gliomas: LRIG1 protein expression decreased in higher grade gliomas.”

In this study by Marlene Happe, Saskia Kuhl, Lukas Görtz, Roland Goldbrunner and Marco Timmer, from the University of Cologne, researchers found that the LRIG1 protein, which may help suppress tumors, is present at lower levels in more aggressive gliomas, a type of brain tumor. The findings suggest that LRIG1 could serve as a useful marker for tumor severity and potentially as a target for future therapies.

Gliomas are the most common malignant brain tumors in adults and carry a poor prognosis, particularly in their most severe form, glioblastoma. This study investigated three related proteins: LRIG1, LRIG2, and LRIG3, which are involved in regulating cell growth signals. While LRIG1 and LRIG3 have shown tumor-suppressing effects in previous studies, LRIG2 is thought to support tumor growth. The researchers analyzed tumor samples from patients to understand how these proteins behave across different glioma grades and how they respond to chemotherapy.

The results showed that LRIG1 protein levels decline significantly as tumor grade increases. Low-grade gliomas displayed much higher LRIG1 expression than high-grade tumors. Among high-grade tumors, primary glioblastomas had the lowest levels of LRIG1. Interestingly, secondary glioblastomas, which typically develop from lower-grade tumors, had higher levels of LRIG1 than primary glioblastomas. This difference may contribute to their relatively better clinical outcomes. These results highlight LRIG1’s potential role in slowing tumor progression.

In contrast, LRIG2 showed a more complex pattern. While its gene expression was higher in lower-grade tumors, the actual protein levels were slightly elevated in higher-grade ones, which are more aggressive. This mismatch suggests that processes occurring after gene transcription may influence how much LRIG2 protein is produced. 

“However, our data on LRIG2 indicate that its role in glioma may be more complex than previously thought, warranting further investigation.”

Concerning LRIG3, it was found in higher amounts in glioma tissue compared to surrounding healthy tissue. Its expression was particularly high in low-grade tumors. However, chemotherapy did not consistently affect LRIG3 levels, and results varied depending on tumor type and treatment status.

Overall, the study suggests that members of the LRIG protein family, especially LRIG1, could serve as important biomarkers to distinguish between glioma types and grades. Although chemotherapy did not significantly change their expression in most cases, these proteins have high potential as diagnostic tools or therapeutic targets. Further research is needed to better understand their roles in glioma development and treatment response.

DOI - https://doi.org/10.18632/oncotarget.28775

Correspondence to - Marco Timmer - marco.timmer@uk-koeln.de

Abstract video - https://www.youtube.com/watch?v=ZHsKLBEyBbM

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Keywords - cancer, oncology, glioma, glioblastoma, LRIG1, LRIG2, LRIG3

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Lower LRIG1 Expression Linked to Aggressive Gliomas

BUFFALO, NY – November 17, 2025 – A new #research perspective was #published in Oncotarget (Volume 16) on November 14, 2025, titled “A personal perspective of patient-centred clinical trials.”

In this perspective, led by corresponding author Jia Liu of The Kinghorn Cancer Centre, St Vincent’s Hospital, the University of New South Wales, and the Garvan Institute of Medical Research, three early-phase clinical trial participants — Trevor Tyne, Elizabeth Ivimey, and Leanne Duggan — reflect on their personal experiences with experimental cancer treatments. Their stories offer a unique perspective on the patient journey through early-phase trials and emphasize the need to design clinical research that prioritizes patients’ needs, dignity, and lived realities. The authors highlight both the life-changing opportunities that trials can provide and the systemic barriers that still prevent many patients from participating.

This perspective captures a turning point in how early-phase trials are viewed. Once considered a last resort, these trials are now increasingly offered earlier in treatment, especially with the rise of biomarker-guided therapies. In this context, the patient experience has become critical. The authors outline key benefits of participation, including access to novel therapies, ongoing medical monitoring, emotional support, and a strong sense of purpose in contributing to future medical advancements. However, they also point out significant challenges, such as restrictive eligibility criteria, high financial and logistical burdens, and communication gaps between patients and trial staff.

“While no trial guarantees success, the level of support, access to innovative therapies, and sense of contribution to medical progress can be profoundly meaningful.” 

Each narrative provides insight into the clinical trial experience. One patient explains how living with a visual impairment required tailored accessibility support throughout the trial process Another shares how genomic testing led to targeted treatment after standard options failed. Despite their different diagnoses and circumstances, all three stories reflect resilience, hope, and a shared call for trial designs that better reflect the realities of diverse patients.

To address these issues, the authors propose a number of improvements to trial design and delivery. These include expanding eligibility criteria, offering financial and logistical assistance, improving communication training for research staff, and introducing dedicated trial navigators to help guide patients through complex processes. They also focus on the importance of involving patient advocates in trial design and ensuring smoother transitions for patients moving between treatment centers.

While early-phase trials focus on safety and effectiveness, the authors argue they must also be guided by core values like ethics and patient empowerment. This perspective serves as a reminder that the future of cancer research depends not only on scientific innovation, but on an honest partnership between patients and the research community.

By sharing these real-world experiences, the article encourages a broader conversation about how to make clinical trials more responsive to the people they are designed to serve.

DOI - https://doi.org/10.18632/oncotarget.28776

Correspondence to - Jia Liu - jia.liu@svha.org.au

Abstract video - https://www.youtube.com/watch?v=2CCGN78n8ug

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Clinical Trial Participants Call for More Inclusive, Patient-Centered Cancer Research

BUFFALO, NY – November 18, 2025 – A new #review was #published in Oncotarget (Volume 16) on November 14, 2025, titled “Mechanism of anticancer action of bifidobacterium: Insights from gut microbiota.”

This review, led by first author Hoang Do and correspondent author Ashakumary Lakshmikuttyamma from Thomas Jefferson University, explores how bifidobacterium, a common probiotic found in the gut, may contribute to cancer prevention and therapy. By analyzing existing studies, the authors highlight the growing importance of gut health in cancer treatment and shed light on how bifidobacterium could complement standard cancer therapies.

Bifidobacterium is widely known for promoting digestive health and is often included in fermented foods and dietary supplements. However, emerging evidence suggests it may also play a broader role in immune regulation and cancer defense. The review explains how certain strains of bifidobacterium may enhance the effectiveness of chemotherapy, radiation, and immunotherapy in cancers such as breast, lung, colorectal, and gastric cancers.

According to the review, bifidobacterium influences cancer outcomes through several biological mechanisms. It helps regulate immune function by reducing inflammation and supporting the activity of immune cells that target tumors. For instance, strains like B. longum and B. breve have been shown to lower levels of harmful inflammatory markers and boost anti-inflammatory responses. These changes can make cancer treatments more effective while also reducing side effects.

“Presence of Bifidobacterium breve in gut microbiota extended the median progression-free survival of NSCLC patients.”

The review also discusses how bifidobacterium helps detoxify the body by breaking down cancer-causing compounds and limiting their ability to damage cells. In preclinical studies, the probiotic reduced the activity of enzymes that produce carcinogens and helped in converting food-based substances into cancer-fighting agents. Some strains were even found to suppress genes that promote tumor growth and increase molecules that trigger cancer cell death.

The authors emphasize that diet plays a critical role in supporting the growth of bifidobacterium. Foods rich in dietary fiber, especially those containing inulin and oligosaccharides like garlic, onions, or leeks, can help increase its levels in the gut. This suggests that simple dietary changes could not only improve gut health but also support cancer prevention and treatment strategies.

Although the review presents compelling evidence, the authors stress the need for more clinical trials to determine how different strains of bifidobacterium affect specific types of cancer. Personalized approaches may be necessary to match the right probiotic strains with individual treatment plans.

As research continues to uncover the link between gut microbes and cancer, bifidobacterium stands out as a promising natural ally that could enhance the body’s defenses and improve cancer treatment outcomes.

DOI - https://doi.org/10.18632/oncotarget.28779

Correspondence to - Ashakumary Lakshmikuttyamma - axl025@jefferson.edu

Abstract video - https://www.youtube.com/watch?v=KTWJDAN15lY
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Probiotic Bifidobacterium May Boost Cancer Treatment and Suppress Tumors

Cancer is a disease caused by the uncontrolled growth of cells that escape the body’s natural defenses. One way cancer protects itself is by taking advantage of certain immune cells called regulatory T cells, or Tregs. Normally, Tregs help prevent autoimmune diseases by controlling the immune system. But inside tumors, they behave differently. Instead of defending the body, they suppress the immune cells that could attack the cancer.

Many cancer treatments aim to activate the immune system to fight tumors more effectively. However, the presence of Tregs within the tumor makes this difficult. These cells act like bodyguards for the cancer, blocking the immune response that might otherwise slow or stop tumor growth.

Researchers have tried to eliminate Tregs by targeting a protein called CD25, found on their surface. However, earlier efforts often failed because these treatments also interfere with interleukin-2 (IL-2), a molecule that is essential for other immune cells to function. Blocking IL-2 weakens the entire immune response, limiting the treatment’s effectiveness.

To overcome this challenge, scientists recently developed a new antibody called 2B010. This study, titled “A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment,” was published in Oncotarget (Volume 16).

Full blog - https://www.oncotarget.org/2025/11/19/new-antibody-removes-tregs-to-boost-immune-response-against-cancer/

Paper DOI - https://doi.org/10.18632/oncotarget.28752

Correspondence to - Ethan M. Shevach - eshevach@Niaid.NIH.gov

Abstract video - https://www.youtube.com/watch?v=2NJcGsI7WXA

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Keywords - cancer, Treg, CD25, TME, mAb, GVHD

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New Antibody Removes Tregs to Boost Immune Response Against Cancer

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We, the scientists, should change the situation and change the policies of Indexes such as Clarivate's Web of Science, and Medline, and make indexes work for us. Otherwise, why should all of these organizations exist?

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Librarians Against Scientists: Oncotarget lesson

Hundreds of scientific studies, reviews, and analyses are being published from around the world at any given time. This can make reading the latest research literature a time consuming task—depending, of course, on the quantity of papers one hopes to consume. As a tool to help alleviate this important undertaking, many researchers have taken to listening to one of the top open-access podcasts of 2020 and 2021: The Oncotarget Podcast.

After a paper is published, it is added to an enhanced post-publication service provided by Oncotarget, in an effort to help authors reach a wider audience. This podcast series is another way to widely distribute the research that is published with free access by Oncotarget. Oncotarget Podcast episodes regularly include audio readings, press releases, and interviews with authors about their latest and trending papers published by Oncotarget. Player.fm (https://player.fm/podcasts/open-access) rated the Oncotarget Podcast on their lists of Best Open Access Podcasts of 2020 and 2021.

Oncotarget, and Impact Journals as a whole, is constantly expanding the definition of open-access to include a wide variety of accessibility-based audio and visual media to support researchers and readers with disabilities. Creators of the Oncotarget Podcast hope that offering audible renderings of literature from Oncotarget.com, and of blog posts from Oncotarget.org and Oncotarget.net, will be helpful for the vision impaired community.

Stay up-to-date with all of the latest oncology-focused research literature published by Oncotarget by subscribing to the Oncotarget Podcast, which can be found on Soundcloud, Apple, Stitcher, and Blubrry podcast streaming services.

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Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Oncotarget Podcast Episodes: The Latest in Oncology-Focused Research

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

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