The p53 protein, often called the “guardian of the genome,” is crucial for preventing cancer by repairing damaged DNA or triggering cell death in cells that cannot be repaired. However, in about half of all cancers, the p53 gene is mutated, making the protein ineffective. A groundbreaking study has introduced PG3, a new compound that restores tumor suppression without relying on p53, offering a new option to treat resistant cancers.

Published in Oncotarget on September 17, 2024, the study titled “Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics,” introduces PG3, a small molecule with a completely new approach to treating cancer. This groundbreaking research was conducted by Dr. Xiaobing Tian and Oncotarget Editor-in-Chief Dr. Wafik S. El-Deiry from Brown University.

The researchers tested PG3 on cancer cell lines with various p53 mutations, as well as on cells that lacked p53 entirely.

Full blog - https://www.oncotarget.org/2024/12/18/a-new-path-to-tumor-suppression-the-promise-of-pg3/

Paper DOI - https://doi.org/10.18632/oncotarget.28637

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

Video short - https://www.youtube.com/watch?v=eBp_UGrkii8

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Keywords - cancer, mutant p53, integrated stress response (ISR), ATF4, HRI, ClpP

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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Oncotarget

A New Path to Tumor Suppression: The Promise of PG3

Joseph Yoo was baptized, raised, and ordained in the United Methodist Church, and is now an Episcopalian priest and the planter of Mosaic Episcopal Church located in the suburbs of Houston, Texas. Joseph is the author of When the Saints Go Flying In: Stories About Faith, Life, and Everything in Between and is known for his dynamic presence on Instagram and TikTok, where he reflects on everything from scripture to social justice to pro wrestling. In this conversation, Joseph and Brandon talk about the curious and winding paths we travel as we follow the spiritual calling of our lives, and the people who, through the unfolding of their lives, teach us about God.  


Host: Brandon Nappi 

Guest: Joseph Yoo 

Instagram: @theleadersway.podcast berkeleydivinity.yale.edu/podcast 

You can support our work at https://tinyurl.com/support-transforming-leaders 

73: It's Okay to Have Jesus & a Therapist with Joseph Yoo

BUFFALO, NY — November 25, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 13, 2025, titled “Hospitalization with infections and risk of Dementia: a systematic review and meta-analysis.”

This large-scale meta-analysis, led by first author Wei Yu Chua from the National University of Singapore and corresponding author Eng-King Tan from the National Neuroscience Institute and Duke-NUS Medical School in Singapore, shows that adults hospitalized with infections have a significantly higher risk of developing dementia. The findings are especially important as global populations grow older and hospitalizations for infections increase, highlighting a potential new approach for dementia prevention.

“Out of 1900 studies that were screened initially, 16 studies comprising 4,266,276 patients were included for analysis.” 

The researchers analyzed data from over 4 million individuals across 16 studies, making this study the most comprehensive review to date on the association between infection-related hospital stays and long-term brain health. The results showed that being hospitalized for an infection raised the risk of all-cause dementia by 83%. Among the types of infections studied, sepsis carried the highest risk, followed by pneumonia, urinary tract infections, and skin or soft tissue infections. The risk of developing vascular dementia was notably higher than that of Alzheimer’s disease.

One possible explanation for the association between infections and dementia is that infections trigger systemic inflammation that may reach the brain. Inflammatory molecules can cross the blood-brain barrier, potentially leading to the buildup of damaging proteins and the death of brain cells. This process may be more severe in older adults, whose immune systems are often slower to respond and recover. The study also suggests that even a single infection-related hospitalization can speed up cognitive decline, especially in individuals already at higher risk.

Importantly, the risk of dementia was greatest within the first year following an infection but remained elevated for many years afterward. In fact, studies with follow-ups longer than a decade showed even stronger associations. These results suggest the need for early cognitive monitoring after hospital discharge, particularly in older adults recovering from infections.

These findings have important implications for healthcare systems, particularly those serving aging populations, and underscore the lasting impact that infections can have on the brain. This research highlights the importance of looking beyond genetics and lifestyle for prevention strategies. With over 50 million people affected by dementia worldwide and annual care costs in the U.S. exceeding $300 billion, identifying new and preventable risk factors is critical. Reducing infections, improving hospital care, and monitoring brain health after illness may offer promising ways to protect cognitive function in aging populations.

DOI - https://doi.org/10.18632/aging.206329

Corresponding author - Eng-King Tan - tan.eng.king@singhealth.com.sg

Abstract video - https://www.youtube.com/watch?v=uyv5VHHHIA4

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Aging-US

Hospital Infections Associated with Higher Risk of Dementia

Interest in healthier, longer lives is rising, supported by recent scientific advances in aging research. But turning those discoveries into everyday healthcare solutions remains a work in progress. In this landscape, longevity clinics have attracted attention as personalized alternatives to traditional medicine.

What Are Longevity Clinics?

Longevity clinics are private centers offering tailored programs designed to improve long-term health and slow biological aging. Using advanced diagnostics such as genetic sequencing, full-body imaging, and blood tests, they develop personalized plans that may include exercise, nutrition, hormone therapy, or experimental treatments. Frequently found in countries like the United States, Switzerland, and the United Arab Emirates, these clinics reflect a growing global interest in preventive healthcare, though their high costs and scientific credibility remain subjects of debate.

The Editorial

“Longevity clinics: between promise and peril,” an editorial by Marco Demaria, Editor-in-Chief of Aging-US, from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), was published in Aging-US (Volume 17, Issue 10). 

Full blog - https://aging-us.org/2025/11/longevity-clinics-balancing-innovation-with-regulation/

Paper DOI - https://doi.org/10.18632/aging.206330

Corresponding author - Marco Demaria — m.demaria@umcg.nl

Abstract video - https://www.youtube.com/watch?v=Bt84xBdii0s

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Keywords - aging, longevity clinics, biomarkers, frailty, senescence

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Longevity Clinics: Balancing Innovation with Regulation

BUFFALO, NY — December 1, 2025 — A new #research paper featured on the #cover of Volume 17, Issue 11 of Aging-US was #published on October 30, 2025, titled “SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16 positive cancer cells.”

In this study led by first author Ryan Wallis along with corresponding author Cleo L. Bishop, from Queen Mary University of London, researchers developed a machine learning tool to identify compounds that induce cancer cells into senescence. The tool, called SAMP-Score, offers a new strategy for drug discovery in cancers with poor treatment options like basal-like breast cancer.

Senescence is a process where damaged or aged cells stop dividing. In cancer therapy, inducing senescence is an approach to control tumor growth. However, it is difficult to detect true senescence in cancer cells that already appear aged. These cancers, often called Sen-Mark+ cancers, include basal-like breast cancer and typically lack reliable markers to confirm senescence. SAMP-Score was designed to address this problem.

Instead of relying on traditional markers, the researchers built a machine learning model trained to recognize patterns based on senescent cells’ shape and structure under a microscope. These visual patterns, known as senescence-associated morphological profiles (SAMPs), allowed the model to distinguish real signs of aging from other effects such as toxicity or normal variation. By analyzing thousands of cell images, the model learned to classify whether a cell had truly entered senescence.

“To demonstrate the potential application of SAMP-Score in p16 positive cancer therapeutic discovery, we assessed a diversity screen of 10,000 novel chemical entities in MB-468 cells (p16 positive BLBC).”

The team used SAMP-Score to screen more than 10,000 experimental compounds. One compound, QM5928, consistently triggered senescence in several cancer cell types without killing them, making it a promising candidate for further study. Importantly, it worked in cancers resistant to known drugs like palbociclib, which are often ineffective in cancers with high p16 expression like basal-like breast cancer. 

Further analysis revealed that QM5928 caused the p16 protein to move into the nucleus of cancer cells, a possible sign that the protein is helping stop cell division. This subtle effect was only detectable using the detailed imaging and analysis made possible by SAMP-Score, highlighting the tool’s ability to distinguish true senescence from toxic responses and making it a powerful resource in cancer drug discovery.

By combining machine learning with high-resolution imaging, this study introduces a new way to find and evaluate cancer therapies. SAMP-Score could accelerate efforts to develop treatments that exploit the body’s natural aging processes to fight cancer, especially for patients with resistant tumors. The tool is openly available at GitHub, making it accessible for other researchers exploring senescence-based cancer therapies.

DOI - https://doi.org/10.18632/aging.206333

Corresponding author - Cleo L. Bishop - c.l.bishop@qmul.ac.uk

Abstract video - https://www.youtube.com/watch?v=qXI_KI3EgHE

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Machine Learning Identifies Senescence-Inducing Compound for p16-Positive Cancer Cells

What does “community” actually mean? Is community something we achieve or is it something we practice? Claire Brown and Austin Sauerbrei are partners, parents, and community practitioners, living and working in small town rural America. Claire is the rector of a small Episcopal church and Austin is a community organizer with the 50+ year-old statewide nonprofit, SOCM. Their daily lives are a whirlwind of tending to relationships and building muscle for faithful community engagement in their small town. With humor, candor, and wisdom honed by years of deep listening, they offer insights about the tensions and opportunities that arise when we acknowledge how intertwined we are with one another. 


This episode is worth watching on The Leader’s Way YouTube channel! In this interview, Austin and Claire model what it looks like to engage in thought-partnership and parenthood, passing their youngest child, Ardy, between them as they respond to host Whitney Kimball Coe’s questions about how we do the thing we call “community.”  


Learn more about The Rev’d Claire Brown: https://www.revclairebrown.com/ 

 
Learn more about Austin Sauerbrei’s new graphic novel, Trouble! At Coal Creek: https://www.haymarketbooks.org/books/2529-trouble-at-coal-creek 

“Have You Met the Community?” with Claire Brown and Austin Sauerbrei

BUFFALO, NY — December 3, 2025 — A new #essay was #published in Volume 17, Issue 11 of Aging-US on November 19, 2025, titled “On the intergenerational transfer of ideas in aging and cancer research: from the hypothalamus according to V.M. Dilman to the mTOR protein complex according to M.V. Blagosklonny.”

In this work, Aleksei G. Golubev from the N.N. Petrov National Medical Research Center of Oncology reflects on the legacy of two influential Russian scientists, Vladimir M. Dilman and his son Mikhail V. Blagosklonny, who each introduced groundbreaking ideas about aging and cancer. Drawing from his own experience working in Dilman’s lab, Golubev explores how their ideas remain deeply relevant to today’s scientific understanding.

The essay connects Dilman’s “elevation theory” with Blagosklonny’s “hyperfunction theory,” two frameworks that challenge the conventional view of aging as a process of decline. Instead, both propose that aging results from continued biological processes that once supported growth but eventually become harmful when left unchecked.

Dilman believed that aging begins with reduced sensitivity in the hypothalamus, a brain region that regulates the body’s balance. This desensitization disrupts metabolism and hormone levels, setting the stage for many chronic illnesses. Decades later, Blagosklonny expanded on this idea at the molecular level. Central to his theory is the mTOR protein complex, which regulates growth and metabolism and is now a major focus in aging research.

Golubev also explores the historical and personal connections between the two scientists. Dilman, an endocrinologist trained in the Soviet Union, and Blagosklonny, a molecular biologist educated during the post-Soviet period, represent two generations shaped by a shared scientific tradition. 

“Dilman’s scientific legacy is not as well recognized as it should be, partly due to bias in citation practices.”

The essay also draws attention to a troubling trend in science: the tendency to overlook early contributions, especially from non-Western scholars. Many of Dilman’s insights, such as the connection between high blood sugar, insulin resistance, and cancer, have since been validated by modern tools, yet his work is rarely cited. Golubev points out how citation practices, language barriers, and historical isolation have contributed to this lack of recognition.

Finally, Golubev encourages the scientific community to look back and acknowledge the foundational work that shaped modern aging science. It also highlights the importance of cross-generational knowledge in moving science forward. By tracing the intellectual journey from hormonal regulation in the brain to molecular pathways in cells, this essay demonstrated the relevance of old ideas in a new biological era.

DOI - https://doi.org/10.18632/aging.206338

Corresponding author - Aleksei G. Golubev - lxglbv@rambler.ru

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

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Keywords - aging, gerontology, history of science, hyperfunction, mTOR, hypothalamus, cancer, metabolism, immunity

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How Two Russian Scientists Changed the Way We Understand Aging and Cancer

Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths globally. While early detection significantly improves outcomes, many patients are diagnosed at advanced stages when treatment options are limited and relapse is common. To address this challenge, researchers are exploring whether existing drugs can be repurposed for cancer therapy, a strategy that could accelerate drug development while reducing associated costs and risks.

One class of drugs under investigation is statins, commonly prescribed to reduce cholesterol and prevent cardiovascular disease. Several studies have observed a potential link between elevated cholesterol and increased CRC risk. Cholesterol may support tumor growth by promoting membrane synthesis and energy metabolism in rapidly dividing cells.

Building on this connection, researchers from leading Indian institutions, including the Indian Institute of Science Education and Research and the Center of Excellence in Epigenetics at Shiv Nadar Institution of Eminence, investigated how statins influence CRC cells at the molecular level. Their goal was to determine whether these widely used drugs could have a therapeutic role in oncology.

The Study: Investigating the Molecular Impact of Statins in CRC Cells

The study, titled “Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer,” was published in Oncotarget (Volume 16). Using a combination of lipidomics, transcriptomics, proteomics, and 3D tumor models, the researchers explored how two widely prescribed statins, atorvastatin and simvastatin, affect molecular pathways associated with CRC progression. This integrative, multi-omics strategy enabled tracing statin-induced effects across different layers of cellular function, linking lipid, transcript, and protein changes to pathway-level shifts.

Full blog - https://www.oncotarget.org/2025/12/03/repurposing-statins-exploring-anti-tumor-effects-in-colorectal-cancer/

Paper DOI - https://doi.org/10.18632/oncotarget.28755

Correspondence to - Sanjeev Galande - sanjeev.galande@snu.edu.in

Abstract video - https://www.youtube.com/watch?v=A95ICULaH3Y

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Keywords - cancer, colorectal cancer, statins, SATB1, Wnt/β-catenin signaling, tumor-suppressive phenotype

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Repurposing Statins: Exploring Anti-Tumor Effects in Colorectal Cancer

Karilyn Larkin, MD, is leading a new clinical trial that could change and improve the way acute myelogenous leukemia (AML) is treated. “AML is a good example of how the better you understand the disease and the more clever you are in designing the clinical trial allows you to start to see successes where there were none before,” said Larkin, a James physician and hematologist. “In the past 10 years there have been more than 10 new drugs approved for treating AML which is phenomenal.” AML is a rare cancer of the blood that spreads quickly. Larkin and her team discovered a novel surface target on AML cells: the CD37 protein. This protein had previously been seen on lymphomas (another type of blood cancer). A drug was developed but wasn’t more effective than the standard of care for treating lymphomas. “We discovered CD37 is expressed more in AML and starts on the surface of the cells and is quickly pulled into the cells and that nuance makes it a good target for delivering a toxic payload [through the drug previously developed for lymphoma].” A clinical trial began in June that included several other major cancer centers around the country. Larkin was the principal investigator. The trial is currently in Phase 1 of its development in which “we start with a low dose and then make incremental increases, and once we find the correct and safe dose we will enter Phase 2 and expand the number of patients in the trial,” Larkin said. This trial a great example of what’s known as the bench to bedside approach in the battle against cancer. Scientists in the lab – or the bench – find new targets and drugs and work with physicians to bring these advances to patients – the bedside.

Episode 201: A New Clinical Trial for Treating Acute Myeloid Leukemia (AML),  with Dr. Larkin

In today’s episode, I talk with a truly special group of scholars, Candace Borders, Alison Kibe, and Jeania Ree Moore. They met as Graduate Writing Fellows and connected by giving each other feedback on their writing. While they share academic fields and methodologies, their ethics of care and investment in each other’s work allowed them to try out a new form of peer-review group, as “group consultations.” Conjoining the structure and duration of a peer-review writing group with the feedback process of an individual consultation, their group offers a unique model that can be formed by grad students who share a department and discipline. Sharing a discipline or department can have its’ challenges with respect to going “too deep” into the content, possible competition, and uneven experiences with working with advisors and gaining access to resources. Our guests offer a pathway based on Black feminist writing practices and theory that can mediate these challenges to offer a truly collaborative, compassionate, and accountable group writing and feedback model. 

Jeania Ree Moore is a writer, clergyperson, and interdisciplinary scholar of theology, religion, and African American studies. She is a PhD candidate in African American Studies and Religious Studies at Yale University, where her research draws on theology, ethics, and related disciplines to engage a range of sites in Black history and culture.  

Alison H Kibbe is an Assistant Professor of African American Studies at the College of Charleston. She is a scholar, multidisciplinary artist, and cultural organizer. In her scholarly work, Alison specializes in critical food studies, Black geographies and Black mobilities, and cultural production across the Caribbean and African Diaspora.

Candace Borders is an interdisciplinary scholar, educator, and curator. Her research explores the intersections of race, gender, class, and the urban Midwest, with particular attention to role of Black women’s activism in shaping the urban landscape.  She is a Postdoctoral Fellow at The Center for the Humanities, Washington University in St. Louis and received her PhD in American Studies and African American Studies from Yale University. 


Synergies, not Thorns:  Sustaining Connection and Writing Support in Shared Disciplines through a “Group Consultation” Peer Model

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/

A New Path to Tumor Suppression: The Promise of PG3

Oncotarget Podcast

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