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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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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Oncotarget

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

BUFFALO, NY — March 5, 2025 — A new #research paper was #published in Aging (Aging-US) on February 11, 2025, Volume 17, Issue 2, titled “Exposome-wide association study of environmental chemical exposures and epigenetic aging in the national health and nutrition examination survey.” 

First author Dennis Khodasevich and corresponding author Andres Cardenas from Stanford University, and colleagues from other U.S. institutions, studied how exposure to harmful chemicals in the environment affects aging. Using data from the National Health and Nutrition Examination Survey (NHANES), they discovered that cadmium, lead, and cotinine are linked to faster biological aging, a process that can increase the risk of age-related diseases.

The study analyzed data from 2,346 U.S. adults aged 50 to 84 who participated in a national health survey. Researchers tested their blood and urine for 64 different chemicals, including metals, pesticides, and industrial pollutants. They assessed how these exposures influenced eight different epigenetic aging markers—biological clocks that measure how fast a person’s body is aging at the DNA level.

"We harnessed data from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles to examine exposome-wide associations between environmental exposures and epigenetic aging."

The strongest effects were linked to cadmium, a toxic metal found in cigarette smoke and some foods. People with higher levels of cadmium in their blood showed signs of accelerated aging. Higher levels of cotinine, a chemical related to tobacco exposure, were also linked to increased biological age, reinforcing the harmful effects of smoking. Additionally, lead exposure, a heavy metal found in old paint and contaminated water, was also associated with faster aging. 

The researchers also found that some pollutants, including a type of PCB (PCB118) and a type of dioxin (HpCDD), were linked to slower biological aging. However, it is unclear if this fact is beneficial, as past research shows that slower aging in some cases can still be linked to health risks.

This study is one of the largest to investigate how pollution affects the aging process. Unlike previous research that focused on only a few chemicals, it examined a wide range of pollutants in a diverse group of people. The findings suggest that everyday exposure to toxic substances can speed up aging at the cellular level, increasing the risk of age-related diseases.

In summary, these findings raise concerns about how widespread environmental contaminants may accelerate aging and contribute to chronic diseases such as heart disease, cancer, and cognitive decline. Reducing exposure to toxic substances like cadmium and lead—found in cigarettes, polluted air, and contaminated food—could help slow biological aging and improve long-term health. These insights highlight the need for stronger environmental health policies to protect individuals from premature aging and disease.

DOI - https://doi.org/10.18632/aging.206201

Corresponding author - Andres Cardenas - andresca@stanford.edu

Video short - https://www.youtube.com/watch?v=WcL-K399a7M

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Aging (Aging-US)

Toxic Environmental Pollutants Linked to Faster Aging and Health Risks in U.S. Adults

Yale SOM grad Bryan Enriquez '21 discusses launching the Hallow prayer app, argues that technology and artificial intelligence are good for religion and religious practice, and responds to critics who say that the marketing of Hallow commercializes faith.

This episode's transcript and more info can be found here: https://divinity.yale.edu/news/quadcast-developing-1-religion-app-world-bryan-enriquez

Developing the #1 religion app in the world with Bryan Enriquez

In this episode, Dr. Suhail Yusuf joins Sindy Yang (MAR ’24) for a conversation about his identity and work as an ethnomusicologist and performing musician. They also dive into discussion about his main instrument, the sarangi, with its rich history and profound cultural connotations. 

Exploring Ethnomusicology, Hindustani Music, and the Sarangi

Radiation therapy or radiotherapy, is a common treatment for cancer, but its effectiveness differs across patients. A recent study published as the cover for Volume 17, Issue 2 of Aging explored why this happens. The findings provide valuable insights, particularly for brain cancers like glioblastoma (GBM) and low-grade gliomas (LGG).

Understanding Glioblastoma and Low-Grade Gliomas

Glioblastoma and LGG are both brain tumors, but they behave in very different ways. GBM is highly aggressive, with most patients surviving only 12 to 18 months, even with surgery, chemotherapy, and radiation therapy. LGG, on the other hand, grows more slowly, and many patients live for decades with proper care.

Despite their differences, LGG and GBM are biologically linked. Some LGG tumors eventually transform into GBM, making early treatment decisions critical. Given radiation therapy’s effectiveness in GBM, it has often been assumed that LGG patients would also benefit from it. However, a new study titled “Variability in radiotherapy outcomes across cancer types: a comparative study of glioblastoma multiforme and low-grade gliomas” challenges this assumption.

Full blog - https://aging-us.org/2025/03/how-radiation-therapy-affects-tumors-glioblastoma-vs-low-grade-gliomas/

Paper DOI - https://doi.org/10.18632/aging.206212

Corresponding author - Morten Scheibye-Knudsen - mscheibye@sund.ku.dk

Video short - https://www.youtube.com/watch?v=j91rzDJHXTE

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Keywords - aging, cancer, biomarkers, radiotherapy, GBM, LGG, survival

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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How Radiation Therapy Affects Tumors: Glioblastoma vs. Low-Grade Gliomas

BUFFALO, NY — March 10, 2025 — A new #research paper was #published in Aging (Aging-US) on February 18, 2025, Volume 17, Issue 2, titled “Transcriptomic landscape of cumulus cells from patients <38 years old with a history of poor ovarian response (POR) treated with platelet-rich plasma (PRP).”

Researchers from IVIRMA New Jersey, Yale School of Medicine, Yale University, and Acibadem Mehmet Ali Aydinlar University studied how a treatment called platelet-rich plasma (PRP) might help women with poor ovarian response. Their results suggest that PRP may enhance ovarian rejuvenation and improve egg quality, potentially increasing pregnancy success rates for women undergoing in vitro fertilization (IVF).

Diminished ovarian reserve is a major challenge in fertility treatments, affecting many women undergoing IVF. It is associated with fewer collected eggs and lower pregnancy success rates. Some studies have explored PRP—a concentration of growth factors derived from a patient’s own blood—as a potential treatment to rejuvenate ovarian function. However, the biological effects of PRP treatment at the molecular level remain unclear.

In this study, the research team, led by first author Leah M. Roberts and corresponding author Emre Seli, analyzed cumulus cells, specialized cells that surround the egg, using RNA sequencing technology. Samples were collected from women aged 18 to 37 with poor ovarian response, who either received PRP therapy or standard treatment before IVF.

The results showed significant differences in gene expression between the two groups. PRP-treated samples exhibited increased activity in genes related to metabolism, cell survival, and communication between cells, all of which are crucial for egg development and fertility. One key finding was that PRP influenced carbohydrate metabolism in cumulus cells. This is essential, as cumulus cells provide energy to the developing egg, and previous research has linked metabolic health to embryo quality. PRP also appeared to regulate pathways related to cell proliferation and programmed cell death, suggesting it may help support egg survival.

“Our findings indicate that PRP treatment regulates certain pathways that could contribute to follicular activation and oocyte maturation.”

Although PRP has been used in medicine for wound healing and tissue repair, its role in fertility treatment is still under investigation. Some clinical trials have shown improved ovarian reserve markers after PRP treatment, while others have not found a direct benefit for pregnancy rates. This study sheds light on how PRP affects cumulus cells, offering valuable insights into its potential for improving fertility treatments.

The researchers hope that further studies will help refine PRP treatments, determine the best protocols, and identify which patients may benefit the most. By understanding the molecular effects of PRP on ovarian cells, scientists may develop targeted fertility therapies to support women facing infertility due to diminished ovarian reserve.

DOI - https://doi.org/10.18632/aging.206202

Corresponding author - Emre Seli - emre.seli@yale.edu

Video short - https://www.youtube.com/watch?v=3Zc_0tr0S84

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

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Platelet-Rich Plasma May Support Ovarian Function in Women with Poor Ovarian Response

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

Video short - https://www.youtube.com/watch?v=kE4XX9ULHBQ

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How Environmental Exposures Affect Genes and Increase Cancer Risk

BUFFALO, NY — March 12, 2025 — A new #research paper was #published in Aging (Aging-US) on February 25, 2025, Volume 17, Issue 2, titled “Epidemiology and genetic determination of measures of peripheral vascular health in the Long Life Family Study.”

Researchers from multiple institutions, led by first author and corresponding author Deidra R. Fricke from the University of Pittsburgh, studied the genetic and lifestyle factors that influence peripheral artery disease (PAD), a condition that restricts blood flow to the legs. Their findings suggest that people from families with exceptional longevity have a lower risk of PAD, possibly due to inherited genetic traits or healthier lifestyle habits.

Peripheral artery disease is a common but often undiagnosed condition that affects millions worldwide. It increases the risk of heart disease, stroke, and mobility issues. This study conducted using data from the Long Life Family Study (LLFS), found that individuals from long-lived families have significantly better vascular health than the general population.

“Peripheral artery disease (PAD) is a major contributor to morbidity in older adults.”

The researchers analyzed over 3,000 participants, including 1,090 long-lived individuals, their 1,554 children, and 362 spouses. Among the oldest participants (average age 89), about 18% had PAD. However, among their children (average age 60), only 1% had PAD—far lower than the expected 12% found in other studies. This finding suggests that certain protective factors, whether genetic or lifestyle-related, help maintain healthier arteries in these families.

In the study, key risk factors for PAD were identified, including aging, high blood pressure, smoking, and hypertension medication use. Interestingly, unlike in other studies, high cholesterol and diabetes were not major risk factors in this group. This data further supports the idea that long-lived families may have genetic protective factors that contribute to better vascular health.

In addition to lifestyle factors, the study found four genomic regions linked to PAD risk. Three of these were new discoveries, while the fourth was similar but not identical to previously published findings. These genetic markers may help scientists better understand why some individuals are more likely to develop PAD and how to prevent it.

“We identified four genomic sites that may harbor variants associated with protection from PAD.”

This research highlights the value of studying long-lived families to unlock the secrets of healthy aging and vascular health. Understanding what helps them maintain better artery function could lead to new strategies for preventing PAD, heart disease, and other age-related conditions.

Paper DOI: https://doi.org/10.18632/aging.206204

Corresponding author: Deidra R. Fricke — der94@pitt.edu

Keywords: aging, ankle-brachial index, peripheral arterial disease, heritability, genomewide linkage analysis, genomewide association study

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About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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Long-Lived Families Show Lower Risk for Peripheral Artery Disease

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

On Being host Krista Tippett reflects on her career and tells stories never before heard on air. She contemplates her grandfather’s spirituality, what she was looking for when she decided to come to Yale Divinity School, the need she saw for intelligent public conversation about spirituality and religion, and the birth story of Speaking of Faith (later On Being) during the Cold War. We consider how religious traditions can open up to the world’s pain and, finally, encourage imaginative, muscular hope.

48: The Subversive Fireside with Krista Tippett

What if a cancer treatment worked—until it suddenly didn’t? A new case report, “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,” published in Oncotarget, reveals how a non-small cell lung cancer (NSCLC) patient developed drug resistance through a rare genetic alteration, allowing the cancer to evade therapy. 

This unexpected finding highlights the importance of advanced genetic testing and personalized cancer treatments.

Non-Small Cell Lung Cancer, Targeted Therapy and Drug Resistance

Non-Small Cell Lung Cancer is the most common type of lung cancer, accounting for nearly 85% of all cases. Some patients with NSCLC have genetic mutations, such as ROS1 gene fusions, that drive tumor growth. These patients often respond well to targeted therapies like lorlatinib, a ROS1 inhibitor that blocks cancer growth.

However, cancer is constantly evolving. Over time, it can develop resistance to targeted therapies, leading to treatment failure. Understanding these resistance mechanisms is crucial for precision oncology, the approach of tailoring cancer treatment based on a patient’s unique genetic profile.

Full. blog - https://www.oncotarget.org/2025/03/12/a-rare-genetic-shift-that-helped-lung-cancer-evade-treatment/

DOI - https://doi.org/10.18632/oncotarget.28682

Correspondence to - Wade T. Iams - wade.t.iams@vumc.org

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

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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A Rare Genetic Shift That Helped Lung Cancer Evade Treatment

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.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

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

Oncotarget Podcast

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