Drug resistance in cancer radiotherapy: From mechanisms to overcoming strategies.

IF 12.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research Pub Date : 2026-09-01 Epub Date: 2026-08-11 DOI:10.1016/j.phrs.2026.108380

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

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引用次数: 0

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.

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肿瘤放疗中的耐药：从机制到克服策略。

放疗常与化疗、靶向治疗和免疫治疗联合使用，以提高肿瘤治疗的疗效。然而，一些耐辐射的癌细胞似乎具有更高的耐药性，导致癌症治疗失败。因此，探索癌症rt耐药机制至关重要。本文概述了癌症rt的分子、细胞和微环境适应。这些适应赋予电离辐射（IR）存活的癌细胞增强的化疗耐药性。此外，RT还激活癌基因信号通路，诱导表观遗传重塑和改变翻译后修饰，共同推动对靶向治疗的抵抗。RT改变肿瘤的内在特性，促进免疫抑制作用，重塑TME，从而诱导免疫治疗抵抗。包括植物化学物质、小分子、合成化合物、大分子、纳米颗粒、光动力疗法（PDT）、光热疗法（PTT）、MicroRNA （miRNA）疗法、PROTACs、过继细胞疗法和工程沙门氏菌在内的各种新兴策略已经被开发出来，以克服癌症rt中的放射耐药和耐药。我们强调评估这些新兴策略的治疗效果和副作用的重要性。本文通过对肿瘤RT耐药机制和新兴策略的总结，旨在明确肿瘤联合治疗的障碍，指导未来肿瘤治疗的研究方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacological research 医学-药学

CiteScore

18.70

自引率

3.20%

发文量

491

审稿时长

8 days

期刊介绍： Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.