Authors
Yang Chen, Chao-Yun Cai, Xiao-Chen Xu, Zheng Yang, Jia Li, Qingming Pan, Lei Wang, Wei Luo, Zhe-Sheng Chen, Leli Zeng, Yihang Pan
Published in
Pharmacological research. Pages 108380. Aug 11, 2026. Epub Aug 11, 2026.
Abstract
Radiotherapy is frequently combined with chemotherapy, targeted therapy and immunotherapy to improve the efficacy of cancer treatment. Nevertheless, some radioresistant cancer cells seem to possess higher drug resistance, leading to failure of cancer treatment. Thus, it is crucial to explore the mechanisms of drug resistance in cancer RT. This review outlines molecular, cellular, and microenvironmental adaptations in cancer RT. These adaptations confer enhanced chemotherapy resistance in cancer cells surviving from ionizing radiation (IR). In addition, RT also activates oncogene signaling pathways, induces epigenetic remodeling and alters post-translational modifications, collectively driving resistance to targeted therapy. RT alters tumor intrinsic properties, promotes immunosuppressive effects and remodels TME, thus inducing immunotherapy resistance. Various emerging strategies including phytochemicals, small molecules, synthetic compounds, macromolecules, nanoparticles, photodynamic therapy (PDT), photothermal therapy (PTT), MicroRNA (miRNA) therapy, PROTACs, adoptive cell therapies, and engineered Salmonella, have been developed to overcome radioresistance and drug resistance in cancer RT. We highlight the importance of evaluating therapeutic effects and side effects of these emerging strategies. Through summarizing mechanisms and emerging strategies for drug resistance in cancer RT, this review aims to clarify obstacles in combined cancer treatment and guide future direction of research on cancer therapy.
PMID:
42580390
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.
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