Qin Shenghui, Schulte Bradley A, Wang Gavin Y
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, United States.
World J Clin Oncol. 2018 Dec 20;9(8):180-187. doi: 10.5306/wjco.v9.i8.180.
Cellular senescence is a form of permanent cell cycle arrest that can be triggered by a variety of cell-intrinsic and extrinsic stimuli, including telomere shortening, DNA damage, oxidative stress, and exposure to chemotherapeutic agents and ionizing radiation. Although the induction of apoptotic cell death is a desirable outcome in cancer therapy, mutations and/or deficiencies in the apoptotic signaling pathways have been frequently identified in many human cancer types, suggesting the importance of alternative apoptosis-independent therapeutic approaches for cancer treatment. A growing body of evidence has documented that senescence induction in tumor cells is a frequent response to many anticancer modalities including cyclin-dependent kinases 4/6 small molecule inhibitor-based targeted therapeutics and T helper-1 cytokine-mediated immunotherapy. This review discusses the recent advances and clinical relevance of therapy-induced senescence in cancer treatment.
细胞衰老 是一种永久性细胞周期停滞的形式，可由多种细胞内在和外在刺激触发，包括端粒缩短、DNA损伤、氧化应激以及接触化疗药物和电离辐射。虽然诱导凋亡性细胞死亡是癌症治疗中期望的结果，但在许多人类癌症类型中经常发现凋亡信号通路中的突变和/或缺陷，这表明癌症治疗中替代凋亡非依赖性治疗方法的重要性。越来越多的证据表明，肿瘤细胞中的衰老诱导是对许多抗癌方式的常见反应，包括基于细胞周期蛋白依赖性激酶4/6小分子抑制剂的靶向治疗和辅助性T细胞1细胞因子介导的免疫治疗。本综述讨论了治疗诱导的衰老在癌症治疗中的最新进展和临床相关性。
