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Research Paper|Volume 17, Issue 2|pp 550—562

Variability in radiotherapy outcomes across cancer types: a comparative study of glioblastoma multiforme and low-grade gliomas

Alexander Veviorskiy1, Garik V. Mkrtchyan2, Andreyan N. Osipov3, Evgeny Izumchenko4, Ivan V. Ozerov4, Alex Aliper1, Alex Zhavoronkov1,5,6,7, Morten Scheibye-Knudsen2
  • 1Insilico Medicine AI Limited, Abu Dhabi, UAE
  • 2Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Denmark
  • 3CANDLE Synchrotron Research Institute, Yerevan 0040, Armenia
  • 4Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL 60637, USA
  • 5Insilico Medicine Hong Kong Limited, Hong Kong Science and Technology Park, Hong Kong
  • 6Insilico Medicine Canada Inc., René-Lévesque Blvd W, Montreal, Quebec H3B 4W8, Canada
  • 7Buck Institute for Research on Aging, Novato, CA 94945, USA
Received: October 16, 2024Accepted: February 3, 2025Published: February 27, 2025

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.

Abstract

Radiotherapy is a crucial treatment option for various cancers. However, the results of radiotherapy can vary widely across different cancer types and even among patients with the same type of cancer. This variability presents a major challenge in optimizing treatment strategies and improving patient survival. Here, we collected radiotherapy phenotype and expression data from 32 TCGA cancer datasets and performed overall survival analysis for 32 cancer types. Additionally, we conducted a signaling pathway enrichment analysis to identify key pathways involved in radiotherapy resistance and sensitivity. Our findings show that radiotherapy improves survival outcomes in certain cancer types, such as glioblasoma multiforme (GBM), while worsening outcomes in others, such as low-grade glioma (LGG). Next, we focused on exploring the differences in radiotherapy outcomes between GBM and LGG, focusing on the molecular mechanisms contributing to these variations. We identify differential regulation of pathways related to programmed cell death, DNA repair, telomere maintenance, chromosome condensation, antiviral responses, and interferon signaling between GBM and LGG patients perhaps explaining radiotherapy efficacy. A genetic analysis confirmed the importance of immune response and radiotherapy outcome for LGG patients. These insights underscore the importance of personalized treatment approaches and the need for further research to improve radiotherapy outcomes in cancer patients.