image: Figure 3. Signaling pathway enrichment analysis results and patients' genetic profiles. (A) Signaling pathways enriched with genes significantly down-regulated in the comparison of IR-treated and untreated GBM patients and simultaneously significantly up-regulated in the comparison of IR-treated and untreated LGG patients. (B) Signaling pathways enriched with genes significantly up-regulated in the comparison of IR-treated and untreated GBM patients and simultaneously significantly down-regulated in the comparison of IR-treated and untreated LGG patients. (C) Venn diagram describing the intersection of genes whose loss/gain status significantly stratifies IR-treated patients. (D) Signaling pathways enriched with genes whose loss status in TCGA-LGG IR-treated patients is associated with worse prognosis. (E) Mutation profile of low-grade glioma cancer tissues in patients receiving radiotherapy.
Credit: Copyright: © 2025 Veviorskiy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“These insights underscore the importance of personalized treatment approaches and the need for further research to improve radiotherapy outcomes in cancer patients.”
BUFFALO, NY — March 3, 2025 — A new research paper was published in Aging (Aging-US) on February 27, 2025, as the cover of Volume 17, Issue 2, titled “Variability in radiotherapy outcomes across cancer types: a comparative study of glioblastoma multiforme and low-grade gliomas.”
An international research team, led by first author Alexander Veviorskiy from Insilico Medicine AI Limited, Abu Dhabi, UAE, and corresponding author Morten Scheibye-Knudsen from the Center for Healthy Aging, University of Copenhagen, investigated how radiotherapy affects survival in different types of cancer, with a special focus on glioblastoma multiforme (GBM) and low-grade gliomas (LGG). Their findings reveal that radiotherapy has opposite effects in GBM and LGG patients. The study highlights key biological differences between these brain cancer types, emphasizing the need for personalized treatment strategies.
Radiotherapy is a standard treatment for many tumors, but its effectiveness varies widely depending on the type of cancer. The researchers began by analyzing data from 32 cancer types using information from The Cancer Genome Atlas (TCGA). They then focused on glioblastoma multiforme (GBM) and low-grade gliomas (LGG), two types of brain cancer with distinct biological behaviors. GBM is an aggressive cancer with poor survival rates, whereas LGG progresses more slowly and often has a better prognosis.
“GBM and LGG are particularly interesting to study together because GBM often originates from a preexisting LGG, representing a progression from a lower-grade to a higher-grade malignancy.”
The results revealed a striking contrast: patients with GBM who received radiotherapy lived longer, whereas those with LGG had shorter survival times after treatment. To understand the reasons behind this, the researchers analyzed gene expression and signaling pathways. They identify several biological processes that may influence radiotherapy outcomes.
For example, GBM tumors have weaker DNA repair mechanisms, making them more vulnerable to radiation-induced damage, which allows radiotherapy to effectively kill cancer cells. In contrast, LGG tumors have stronger DNA repair systems, helping cells survive radiation better and potentially reducing the treatment’s effectiveness. Additionally, differences in immune system activity and genetic mutations—such as EGFR alterations—were linked to worse survival in LGG patients who received radiotherapy.
These findings highlight the need for a more personalized approach to treating brain cancer. The study proposes that a universal approach to radiotherapy is not appropriate, particularly for patients with LGG. Instead, personalized treatment strategies based on genetic and molecular characteristics could improve patient survival outcomes. The research also raises the possibility of combining radiotherapy with targeted therapies, such as immune-boosting therapies or DNA repair inhibitors, to enhance its effectiveness.
In conclusion, this study highlights the complexity of brain cancer treatment and the need for further research to refine therapeutic strategies. By understanding the molecular and genetic differences between the different types of cancers, more effective and personalized approaches can be developed to improve survival and quality of life for brain cancer patients.
Read the full paper: DOI: https://doi.org/10.18632/aging.206212
Corresponding author: Morten Scheibye-Knudsen — mscheibye@sund.ku.dk
Keywords: aging, cancer, biomarkers, radiotherapy, GBM, LGG, survival
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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
Not applicable
Article Title
Variability in radiotherapy outcomes across cancer types: a comparative study of glioblastoma multiforme and low-grade gliomas
Article Publication Date
27-Feb-2025
COI Statement
Insilico Medicine is a company developing an AI-based end-to-end integrated pipeline for drug discovery and development and engaged in aging and cancer research. AV, AA, and AZ are affiliated with Insilico Medicine or were affiliated with Insilico Medicine when the studies were performed. No other conflicts are reported.