Ling Rui, Wang Jingzhi, Fang Yuan, Yu Yunpeng, Su Yuting, Sun Wen, Li Xiaoqin, Tang Xiang
Department of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Department of Radiotherapy Oncology, Affiliated Yancheng First Hospital of Nanjing University Medical School, First People's Hospital of Yancheng, Yancheng, China.
Front Oncol. 2023 Jul 12;13:1193637. doi: 10.3389/fonc.2023.1193637. eCollection 2023.
Radiotherapy is an important means of tumor treatment, but radiotherapy resistance has been a difficult problem in the comprehensive treatment of clinical tumors. The mechanisms of radiotherapy resistance include the repair of sublethal damage and potentially lethal damage of tumor cells, cell repopulation, cell cycle redistribution, and reoxygenation. These processes are closely related to the regulation of epigenetic modifications. Histone deacetylases (HDACs), as important regulators of the epigenetic structure of cancer, are widely involved in the formation of tumor radiotherapy resistance by participating in DNA damage repair, cell cycle regulation, cell apoptosis, and other mechanisms. Although the important role of HDACs and their related inhibitors in tumor therapy has been reviewed, the relationship between HDACs and radiotherapy has not been systematically studied. This article systematically expounds for the first time the specific mechanism by which HDACs promote tumor radiotherapy resistance and and the clinical application prospects of HDAC inhibitors, aiming to provide a reference for HDAC-related drug development and guide the future research direction of HDAC inhibitors that improve tumor radiotherapy resistance.
放射治疗是肿瘤治疗的重要手段，但放射抗拒一直是临床肿瘤综合治疗中的难题。放射抗拒的机制包括肿瘤细胞亚致死性损伤和潜在致死性损伤的修复、细胞再增殖、细胞周期再分布以及再氧合。这些过程与表观遗传修饰的调控密切相关。组蛋白去乙酰化酶（HDACs）作为癌症表观遗传结构的重要调节因子，通过参与DNA损伤修复、细胞周期调控、细胞凋亡等机制，广泛参与肿瘤放射抗拒的形成。尽管HDACs及其相关抑制剂在肿瘤治疗中的重要作用已有综述，但HDACs与放射治疗之间的关系尚未得到系统研究。本文首次系统阐述了HDACs促进肿瘤放射抗拒的具体机制以及HDAC抑制剂的临床应用前景，旨在为HDAC相关药物研发提供参考，并指导未来提高肿瘤放射抗拒的HDAC抑制剂的研究方向。
