REVIEW article
Front. Oncol.
Sec. Radiation Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1642100
This article is part of the Research TopicDNA Damage, Repair and Mutagenesis: Targeting Cancer’s Achilles HeelView all 8 articles
The interplay between DNA damage response and mitochondrial dysfunction in radiotherapy
Provisionally accepted
- 1School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- 2Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- 3Wenzhou key Laboratory of basic science and translational research of radiation oncology, Wenzhou, Zhejiang, 325000, China
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Radiotherapy plays a crucial role in cancer management by directly eliminating cancer cells, reducing the likelihood of recurrence and metastasis, and preserving the functionality of essential organs. Nonetheless, the radioresistance of cancer cells in radiotherapy poses a significant challenge. The DNA damage response (DDR) serves as a protective mechanism against DNA damage, associating with various intrinsic factors and significantly contributing to radioresistance. Furthermore, the function and status of mitochondria are closely linked to the resistance of cancer cells to radiotherapy. The effects of radiation on nuclear and mitochondrial structures are not independent; they interact through bidirectional signaling pathways to affect cellular radioresistance. This review summarizes and discusses the regulatory mechanisms of DDR and mitochondrial function in radiotherapy from the perspectives of anterograde and retrograde signaling, aiming to provide valuable insights into how cells respond to radiation to determine their fate, and to offer new strategies for precise radiosensitization through the coordinated regulation of nuclear-mitochondrial signaling networks in the future.
Keywords: Radiotherapy1, DNA damage response2, mitochondrial dysfunction3, anterograde signaling4, retrograde signaling5
Received: 06 Jun 2025; Accepted: 30 Sep 2025.
Copyright: © 2025 Yang, Li, Zhang, Shen, Hu and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Junfang Yan, yanjf114072@wmu.edu.cn
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