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Interactions between radiotherapy resistance mechanisms and the tumor microenvironment

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机构： [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China. [2]Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. [3]Department of Urology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China. [4]Department of Pathology, Ningbo Clinical Pathology Diagnosis Center, Ningbo, Zhejiang 315211, China. [5]Faculty of Health and Life Sciences, University of Bristol, Bristol, BS8 1TD, UK. [6]Department of Public Research Platform, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China. [7]Division of Surgery & Interventional Science, University College London, London, UK; Basic and Translational Cancer Research Group, Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria, Eastern part of Nigeria, Nsukka, Enugu, Nigeria. [8]Division of Surgery & Interventional Science, University College London, London, UK. [9]Department of Urology, Kyung Hee University, South Korea. [10]Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region of China. Electronic address: williamcscho@gmail.com. [11]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China; Division of Surgery & Interventional Science, University College London, London, UK. Electronic address: dechao.feng@ucl.ac.uk. [12]Division of Surgery & Interventional Science, University College London, London, UK. Electronic address: s.heavey@ucl.ac.uk.

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Resistance to radiotherapy (RT) presents a significant clinical challenge in management of cancer. Recent evidence points to specific mechanisms of resistance within the tumor microenvironment (TME), which we aim to discuss, with the aim of overcoming the clinical challenge.We performed the narrative review using PubMed and Web of Science databases to identify studies that reported the regulative network and treatments of RT resistance from TME perspectives.RT significantly changes the immune TME of cancers, which is closely appearing to play a key role in RT resistance (RTR) by modulating immune cell infiltration and function. Various phenotypes are involved in the development of RTR, such as autophagy, senescence, oxidative stress, cell polarization, ceramide metabolism, and angiogenesis in the TME. Key genes and pathways are also implicated in RTR, including immune and inflammatory cytokines, TGF-β, P53, the NF-κB pathway, the cGAS/STING pathway, the ERK and AKT pathway, and the STAT pathway. Based on the mechanism of RTR in the TME, many proposed routes to overcome RTR, several specifically target the TME including targeting fibroblast activation protein, exosomes management, nanomedicine, and immunotherapy. Many challenges in RT resistance still need to be further explored with emerging investigative methods, such as artificial intelligence, genetic technologies, and bioengineering.The complex interactions between RT and TME significantly affect the efficiency of RT. Novel approaches to overcome this clinical difficulty are promising, which needs future work to further explore and identify better treatment strategies.Copyright © 2025 Elsevier B.V. All rights reserved.

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出版当年[2025]版中科院分区表Review为是的期刊