image: Figure 6. ABT-263 dampens low- and high-LET radiation-induced oncogenic β-catenin signaling. (A) Representative micrographs of active-β-catenin immunostained intestinal tissue sections. (B) Representative micrographs of cyclinD1 immunostained intestinal tissue sections. (C) Quantification of active-β-catenin-stained images. Quantitative data presented as mean ± SEM, and * depicts a statistically significant difference (p<0.05) between the indicated groups. (D) Quantification of cyclin D1-stained images. Quantitative data presented as mean ± SEM and * depicts a statistically significant difference (p<0.05) between the indicated groups. (E) Schematic summary of mechanisms of ABT-263-mediated prevention of IR-induced GI tumorigenesis in Apc1638N/+ mice.
Credit: Copyright: © 2025 Kumar et al.
“Our results offer ‘proof of concept’ for the future use of a pharmaceutical senolytic strategy to reduce the risk of IR-induced GI cancer.”
BUFFALO, NY—February 18, 2025 — A new research paper was published by Aging (Aging-US) on January 8, 2025, in Volume 17, Issue 1, titled “Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development in Apc1638N/+ mice.”
Researchers Kamendra Kumar, Bo-Hyun Moon, Santosh Kumar, Jerry Angdisen, Bhaskar V.S. Kallakury, Albert J. Fornace Jr., and Shubhankar Suman from Georgetown University Medical Center explored whether a drug called ABT-263 could help reduce the risk of gastrointestinal (GI) cancer caused by radiation exposure. Their findings suggest that ABT-263, a senolytic agent, helps eliminate harmful aging cells in the gut, reducing inflammation and lowering cancer risk in mice. These results could lead to potential treatments for people exposed to radiation, including cancer patients and astronauts.
Radiation exposure, whether from medical treatments, environmental sources, or space travel, can damage cells and increase the risk of GI cancer. One key factor in this process is cellular senescence, where damaged cells stop dividing but continue to release harmful molecules that promotes tumor growth. This study tested whether ABT-263, a drug designed to remove these aged cells, could lower cancer risk in a mouse model of GI cancer.
In this study, researchers exposed mice to radiation and found that it increased the number of damaged cells in their intestines, leading to more tumors. However, when the mice were given ABT-263, the number of harmful cells decreased, and they developed fewer tumors. The drug also reduced inflammation and blocked signals that promote cancer growth.
“Oral administration of ABT-263 in Apc1638N/+ mice resulted in a significant reduction in low-LET IR-induced intestinal tumor burden at 5 months post-exposure.”
These findings highlight the potential of senolytic drugs like ABT-263 as a preventive treatment for radiation-induced cancers. This approach could be especially beneficial for cancer patients undergoing radiation therapy, astronauts exposed to cosmic radiation, and individuals at risk from environmental sources such as radon gas.
However, while ABT-263 showed promise, it also has known side effects, including reduced platelet counts, which can impact blood clotting. Future research will focus on optimizing senolytic treatments to ensure they are both safe and effective for human use. Scientists are also exploring alternative drugs and combination therapies that might offer the same benefits with fewer risks.
This study provides strong evidence that removing senescent cells could help prevent radiation-related GI cancer. With further research, senolytic drugs may become an important tool in protecting at-risk populations from the long-term effects of radiation exposure.
Read the full paper: DOI: https://doi.org/10.18632/aging.206183
Corresponding author: Shubhankar Suman – ss2286@georgetown.edu
Keywords: aging, senescence-associated secretory phenotype, senolytic agent, carcinogenesis, inflammation, β-catenin
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About Aging:
The journal Aging 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.)
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development in Apc1638N/+ mice
Article Publication Date
8-Jan-2025
COI Statement
The authors do not have any apparent conflicts of interest concerning this article. The funders were not involved in the planning, execution, or decision to publish the findings.