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 - August 13, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 29, 2025, titled “PCAIs stimulate MAPK, PI3K/AKT pathways and ROS-Mediated apoptosis in aromatase inhibitor-resistant breast cancer cells while disrupting actin filaments and focal adhesion.”

In this study, led by first author Jassy Mary S. Lazarte and corresponding author Nazarius S. Lamango from Florida A&M University College of Pharmacy and Pharmaceutical Sciences, researchers investigated a new class of compounds called polyisoprenylated cysteinyl amide inhibitors (PCAIs) as a potential treatment for aromatase inhibitor (AI) therapy resistant breast cancer. Aromatase inhibitors are a common treatment for estrogen receptor-positive (ER+) breast cancer, but many patients eventually develop resistance, leaving fewer therapeutic options.

The study focused on a PCAI compound called NSL-YHJ-2-27, which was tested in long-term letrozole-treated breast cancer cells (LTLT-Ca), an experimental model of AI therapy resistance. NSL-YHJ-2-27 activated two major signaling pathways, MAPK and PI3K/AKT. Although these pathways typically support cancer cell survival, their overstimulation by PCAIs led to increased oxidative stress, damaging the cells and inducing cell death by apoptosis. The compound also reduced levels of RAC1 and CDC42, proteins involved in maintaining cell shape and movement. These alterations resulted in cytoskeletal disruption and reduced structural integrity, making the cancer cells more vulnerable and less capable of spreading. Importantly, the effects of NSL-YHJ-2-27 persisted after the compound was removed, suggesting long-term control over AI resistant cancer cells may be possible.

“PCAIs inhibited cell proliferation and colony formation by 95% and 74%, respectively, increased active caspase 7 and BAX 1.5-fold and 56%, respectively. NSL-YHJ-2-27 (10 μM) induced LTLT-Ca spheroid degeneration by 61%.”

As a new class of targeted molecules, PCAIs represent an innovative approach distinct from traditional endocrine therapies. Their ability to affect multiple cellular mechanisms simultaneously makes them promising candidates for future drug development.

Overall, this study presents a promising new approach for treating AI therapy-resistant breast cancer. By targeting cellular pathways that support survival and mobility, PCAIs like NSL-YHJ-2-27 could provide a novel strategy to manage advanced or resistant forms of the disease. Further research, including in vivo studies and clinical trials, will be essential to confirm these findings and evaluate their therapeutic potential.

DOI - https://doi.org/10.18632/oncotarget.28759

Correspondence to - Nazarius S. Lamango - nazarius.lamango@famu.edu

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Keywords - cancer, PCAIs, ROS, MAPK, PI3K/AKT, LTLT-Ca cells

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New Compound Disrupts Survival Pathways in Aromatase Inhibitor-Resistant Breast Cancer Cells

BUFFALO, NY — August 14, 2025 — A new #research paper was #published in Volume 17, Issue 7, of Aging (Aging-US) on July 3, 2025, titled “Frailty associates with respiratory exacerbations and mortality in the COPDGene cohort.”

In this study, led by first author Eleanor Kate Phillips from Brigham and Women’s Hospital and corresponding author Dawn L. DeMeo from Brigham and Women’s Hospital and Harvard Medical School, researchers investigated how frailty impacts lung health and survival in individuals with a history of cigarette smoking. They found that frailty raises the risk of lung attacks and death, even in smokers with preserved lung function. This result shows why all current and former smokers should be checked for frailty.

Frailty is a condition that makes the body more vulnerable to illness, especially in older adults. This study focused on more than 2,600 adults with a history of heavy smoking, many of whom showed no signs of lung damage on standard tests. At the second follow-up visit, participants were categorized as robust, prefrail, or frail and followed for about three years. Researchers tracked how often they experienced respiratory attacks, such as episodes of severe coughing or breathlessness, and whether they survived during that period.

“COPDGene is a cohort study of individuals aged 45–80 with a minimum 10 pack-year smoking history.”

The results showed that people who were frail had a three- to five-fold higher chance of developing serious or frequent respiratory attacks compared to those who were robust. These risks were not limited to people with chronic lung disease. In fact, many frail participants with normal lung function still faced a significantly higher chance of lung attacks and death. Even those in the “prefrail” stage, a milder form of frailty, were more likely to experience health complications.

The research team also found that frailty was associated with an accelerated pace of biological aging, measured using a DNA-based test called DunedinPACE. This supports the idea that frailty may reflect deeper biological changes in the body that go beyond what traditional lung function tests can detect. These findings challenge the idea that standard lung tests can rule out future respiratory complications in people with a history of smoking. 

Altogether, the study shows that simple frailty checks could help identify early health problems, allowing for timely interventions that may prevent hospitalizations and potentially save lives. The study suggests that frailty screening may be a valuable tool in public health efforts to reduce respiratory disease and improve outcomes for aging adults.

DOI - https://doi.org/10.18632/aging.206275

Corresponding author - Dawn L. DeMeo - redld@channing.harvard.edu

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Keywords - aging, frailty, cigarette smoking, respiratory exacerbations, COPD, epigenetic aging

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Frailty Linked to Higher Risk of Respiratory Complications and Death in Smokers

Pelotonia is where memories are made. In this episode, co-hosted by David John, MD, we asked several members of the James team who participate in this annual bike ride that has raised more than $300 million for research here at the James to share their favorite Pelotonia memories. For Robert Baiocchi, MD, “one of the coolest memories is seeing one my patients who was still in the midst of treatment zip by me like I was standing still.” Baiocchi has ridden every year and his son has joined him in recent years. Pelotonia is also a family affair for Marisa Bittoni, PhD. She rides with her husband and their two daughters. “One of the best moments in my life, an emotional moment, was crossing the finish line on the 100-mile ride. It was an amazing to cross the finish line together with everyone cheering.” Deb Sundi, MD, said he’s inspired by the other riders, especially the cancer survivors who ride, as well as the volunteers and the thousands of people cheering the riders along the route and at the different finishes. “It gives me an incredible surge of emotion and energy, and I’m truly overwhelmed by the moment.” Laura Schoettmer has been a volunteer at the James and Pelotonia for several years and began riding after her cancer diagnosis and treatment at the James. “I finished treatment in August and rode later that August. And then, the second time I rode, my daughter organized a [surprise] party of several friends and family members at the finish line.”
David Cohn, MD, the James chief operating officer and chief medical officer has ridden in every Pelotonia. “The way Pelotonia connects us with the community is remarkable,” he said. “And the money we raise allows us to do things other institutions can’t do and to be increasingly more competitive in pursuing federal funding.” Cohn added his wife and daughter are Pelotonia volunteers and he rides with his son.

Episode 194: My Favorite Pelotonia Memory, co-hosted by David Cohn, MD

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

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

A prospective student’s high school transcript is the most important individual component of an application. Hannah and Mark discuss what admissions officers look for when reviewing transcripts and how transcripts demonstrate an applicant’s academic preparedness and academic resourcefulness. They share advice on building a high school course schedule and how to navigate the challenges that inevitably arise when students are unable to enroll in their preferred courses. The hosts share answers to some of the most frequently asked questions and give their advice on how to keep a healthy perspective on often-fraught topics such as mathematics placement and maximizing advanced courses.    

Selecting High School Courses

BUFFALO, NY — August 19, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 7, 2025, titled “Epigenetic age and accelerated aging phenotypes: a tumor biomarker for predicting colorectal cancer.”

In this study led by Su Yon Jung from the University of California, Los Angeles, researchers found a strong association between accelerated epigenetic aging and an increased risk of colorectal cancer in postmenopausal women. The study also indicated that lifestyle factors influence this risk.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide, particularly in people over the age of 50. However, individuals do not all age at the same biological rate. Two people of the same chronological age can differ in their biological aging, which reflects the condition of their cells and tissues. This study focused on a specific measure of biological aging known as epigenetic aging, which is based on chemical changes to DNA.

The researchers used data from the Women’s Health Initiative Database for Genotypes and Phenotypes (WHI-dbGaP), which includes genetic and health information from postmenopausal white women aged 50 to 79. They applied three established “epigenetic clocks” to estimate epigenetic age from blood samples collected up to 17 years before a colorectal cancer diagnosis. These clocks measure how quickly a person is aging at the molecular level by tracking DNA methylation. Women with a higher epigenetic age than expected were significantly more likely to develop colorectal cancer

“[…]we examined biological aging status in PBLs via three well-established epigenetic clocks—Horvath’s, Hannum’s and Levine’s […].”

The study also explored the role of lifestyle in modifying this risk. Women who consumed more fruits and vegetables showed no increased risk, even if they were epigenetically older. In contrast, women with both lower fruit and vegetable intake and signs of accelerated aging were up to 20 times more likely to develop colorectal cancer. This suggests that a healthy diet may help reduce cancer risk associated with biological aging.

Another key finding involved women who had both ovaries removed before natural menopause. These women had a higher epigenetic age and, when combined with accelerated aging, a greater likelihood of developing colorectal cancer. This highlights the potential influence of hormonal and reproductive factors on aging and disease risk.

The researchers validated their findings across several independent datasets, supporting the potential of blood-based epigenetic aging markers as early indicators of colorectal cancer risk. These markers could help guide early detection and prevention strategies in aging populations. However, the authors emphasize the need for independent large-scale replication studies.

Overall, this study contributes to a better understanding of the association between epigenetic aging and cancer. It also supports the idea that modifiable lifestyle factors may reduce disease risk, even among those aging more rapidly at the cellular level.

DOI - https://doi.org/10.18632/aging.206276

Corresponding author - Su Yon Jung - sjung@sonnet.ucla.edu

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Epigenetic Aging Markers Predict Colorectal Cancer Risk in Postmenopausal Women

A new #study published as the #cover of Aging (Aging-US) Volume 17, Issue 7, explores how factors in young human blood may affect the biological age of human skin. Researchers from Beiersdorf AG, Research and Development Hamburg in Germany, used a microphysiological co-culture system—a lab-based model simulating human circulation—to test the effects of young versus old blood serum on skin cells. The findings suggest that bone marrow-derived cells play a key role in converting blood-borne signals into effects that support skin rejuvenation.

Understanding Skin Aging and Systemic Influence

As we age, the skin’s ability to regenerate declines, while its biological age increases. This contributes to visible signs of aging and a weakened barrier function. While cosmetic treatments can improve appearance, they rarely target the cellular processes underlying skin aging.

Animal studies have shown that exposure to young blood can promote tissue repair and rejuvenation, likely due to molecules circulating in the bloodstream. However, reproducing these effects in human skin has proven difficult. Applying young serum directly to skin tissue has not produced significant results, indicating that additional cellular interactions may be required.

Full blog - https://aging-us.org/2025/08/skin-rejuvenation-how-young-blood-and-bone-marrow-influence-it/

Paper DOI - https://doi.org/10.18632/aging.206288

Corresponding author - Elke Grönniger - elke.groenniger@beiersdorf.com

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Keywords - aging, skin rejuvenation, microphysiological systems, systemic factors, bone marrow model, human serum

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Skin Rejuvenation: How Young Blood and Bone Marrow Influence It

BUFFALO, NY – August 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 19, 2025, titled “The SCD1 inhibitor aramchol interacts with regorafenib to kill GI tumor cells in vitro and in vivo.”

In this study, led by first authors Laurence Booth and Michael R. Booth, along with corresponding author Paul Dent from Virginia Commonwealth University, researchers investigated how aramchol, a drug originally developed for liver disease, works with the cancer drug regorafenib in gastrointestinal (GI) tumor cells. They found that the combination is effective, especially in tumor cells with a specific genetic variant. The combined approach offers a potential new strategy for treating liver and colon cancers.

Gastrointestinal cancers, such as liver and colon cancer, are serious global health challenges. Regorafenib, already approved for cancer treatment, can have limited impact and frequently causes side effects. Aramchol, a drug developed to treat fatty liver disease, affects how cancer cells process fats and energy. In this study, researchers tested whether combining these two drugs could improve GI cancer treatment, both in cells and mouse models.

The results showed that the drug combination killed liver and colorectal cancer cells more effectively than either drug alone. In animal models, mice with human liver tumors had slower tumor growth, without showing signs of weight loss or other toxicity. 

The researchers also found that aramchol and regorafenib work together to block important survival pathways inside cancer cells. This combination was especially effective in cells with a genetic variant called ATG16L1 T300, which is more common in people of African ancestry. The treatment triggered stress responses in the cancer cells and disrupted key proteins required for survival. It also activated autophagy, a natural recycling process that clears out damaged parts, eventually leading to cancer cell death.

“Aramchol interacted with the multi-kinase inhibitors sorafenib, regorafenib or lenvatinib, to kill GI tumor cells, with regorafenib exhibiting the greatest effect.”

Aramchol is currently in clinical trials for fatty liver disease and has a well-established safety profile, while regorafenib is already FDA-approved for cancer treatment. Together, their combination could advance fast into clinical testing for patients with GI cancers. However, researchers note that additional studies are needed to support the launch of early-phase clinical trials.

Altogether, this study may offer a more effective and less toxic alternative to current treatments for GI cancers. It also highlights the role of genetic variants in shaping treatment response, suggesting that future therapies could be more precisely tailored to each patient’s unique genetic profile.

DOI - https://doi.org/10.18632/oncotarget.28762

Correspondence to - Paul Dent - paul.dent@vcuhealth.org

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Keywords - cancer, macroautophagy, flux; ER stress, aramchol, regorafenib

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Aramchol Boosts Regorafenib Effectiveness in Gastrointestinal Tumors

BUFFALO, NY — August 21, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 17, 2025, titled “The influence of cancer on a forensic age estimation tool.”

In this study by Charlotte Sutter, Daniel Helbling, Cordula Haas and Jacqueline Neubauer from the Zurich Institute of Forensic Medicine, University of Zurich and Onkozentrum Zurich, the researchers investigated how cancer might affect the accuracy of forensic tools used to estimate a person’s age from blood samples.

DNA methylation is a natural chemical modification of DNA that changes with age. Forensic scientists can use these changes to predict someone’s age from biological traces, such as blood found at a crime scene. However, medical conditions like cancer can alter these patterns and potentially reduce the accuracy of such predictions. This study investigated whether various cancer types influence the DNA markers used in age estimation.

“Our study is among the first to show whether it might be necessary to account for the influence of cancer on forensic age estimation tools in order to enhance estimation accuracy as much as possible.”

The researchers applied the VISAGE enhanced age estimation tool, a widely used DNA methylation-based method, to blood samples from 100 cancer patients and 102 healthy individuals. Age predictions in the control group were generally accurate, with small average errors. Patients with solid tumors, including breast and lung cancers, showed only slightly less accurate results. In contrast, individuals with blood cancers, particularly chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), sometimes had large errors, with ages overestimated by as much as 50 years. 

Despite these few extreme cases, the study found that cancer does not typically have a strong impact on the accuracy of this forensic tool. Most cancer patients, even those undergoing treatment, had DNA methylation patterns similar to those of healthy individuals. The researchers found no consistent differences based on cancer type, stage, or treatment, except in isolated cases involving aggressive forms of cancer.

The findings support the continued use of current forensic age estimation methods. While aggressive cancers may occasionally affect prediction accuracy, such cases are rare. The researchers suggest noting these conditions as a possible factor in unusually large errors, without requiring changes to standard practice.

This study provides valuable information about how health conditions, such as cancer, may influence DNA-based age estimation. It strengthens confidence in the reliability of forensic age prediction tools, even when applied to individuals with a medical history of cancer.

DOI - https://doi.org/10.18632/aging.206281

Corresponding author - Cordula Haas - cordula.haas@irm.uzh.ch

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Keywords - aging, forensic age, estimation age prediction, cancer, DNA methylation, age acceleration

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Impact of Cancer on Forensic DNA Methylation Age Estimation

BUFFALO, NY — August 26, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 21, 2025, titled “Association of DNA methylation age acceleration with digital clock drawing test performance: the Framingham Heart Study.”

In this study, led by first author Zexu Li from the Department of Anatomy and Neurobiology at Boston University Chobanian and Avedisian School of Medicine, and corresponding author Chunyu Liu from Boston University Chobanian and Avedisian School of Medicine and Boston University School of Public Health, researchers found that individuals with signs of faster biological aging had lower scores on a digital cognitive test taken seven years later. The findings suggest that the rate at which a person ages at the molecular level may be associated with how well their brain functions as they grow older.

Using data from the Framingham Heart Study, the researchers examined the relationship between biological aging and cognitive health. They used DNA methylation (DNAm) patterns—chemical changes that occur in the DNA with aging, known as epigenetic aging—to estimate biological age acceleration, and used the digital Clock Drawing Test (dCDT) to assess cognitive performance. The dCDT is a computerized version of a traditional pen-and-paper test that evaluates memory, thinking speed, and motor control. It provides an overall score and measures performance in specific areas such as spatial reasoning and movement.

Among 1,789 participants, higher levels of epigenetic age acceleration were associated with significantly lower cognitive scores, particularly those over age 65. Of all the epigenetic aging markers examined, the DunedinPACE measure showed the strongest association with reduced brain function in both younger and older adults. Other measures, such as Horvath and PhenoAge, were associated with lower scores only in older adults. Key areas affected included motor skills and spatial reasoning.

The researchers also studied blood-based protein markers used in an aging measure called GrimAge. Two proteins, PAI1 and ADM, were closely associated with lower cognitive scores, especially in older individuals. These results suggest that declines in brain and motor functions may reflect broader aging-related changes throughout the body.

“Digital cognitive measures displayed stronger associations with most DNAm aging metrics among older compared to younger participants, likely to reflect the cumulative and nonlinear age influences on both brain health and DNAm.”

This study supports the idea that epigenetic age may be a more accurate predictor of cognitive decline than chronological age. The dCDT, which is easy to use, automated, and more precise than traditional tools, may help detect early signs of brain aging. When combined with DNAm measures, it could become a valuable part of regular health screenings.

Overall, the findings provide strong evidence that faster biological aging is associated with cognitive decline. This research may lead to better ways of identifying and monitoring brain health in aging populations.

DOI - https://doi.org/10.18632/aging.206285

Corresponding author - Chunyu Liu - liuc@bu.edu

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