The Dynamic Process and Its Dual Effects on Tumors of Therapy-Induced Senescence.
The Dynamic Process and Its Dual Effects on Tumors of Therapy-Induced Senescence.
复制标题
治疗诱导衰老的动态过程及其对肿瘤的双重影响
DOI：
10.2147/cmar.s285083
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发表时间：
2020
影响因子：
3.3
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Liao C;Xiao Y;Liu L
摘要细胞衰老通常被认为是细胞周期停滞的稳定状态，同时伴随着一系列细胞因子和生长因子的产生。癌细胞响应于化学治疗剂、放射治疗和分子靶向治疗而经历衰老。这种形式的衰老被称为治疗诱导的衰老（TIS），代表了癌症治疗中的理想靶点。最近的研究表明，细胞衰老是一个高度异质性和动态的过程。除了被免疫系统清除外，衰老的癌细胞还可以存活很长时间并摆脱衰老状态。值得注意的是，这些细胞甚至有可能恢复干细胞样状态，具有高侵袭性，最终促进癌症复发。此外，衰老细胞的衰老相关分泌表型（SASP）并不总是相同的，并且可以建立免疫抑制和促肿瘤微环境。考虑到这些不利影响，出现了衰老诱导化疗，然后是衰老疗法（“一击两拳”方法）。这种联合治疗可以减轻持续衰老细胞不必要的副作用，降低促衰老治疗的毒性，延长癌症患者的生存期，在癌症的精确治疗中具有潜在的应用前景。在此，我们回顾了治疗诱导衰老在癌症中的复杂作用，并强调了两步策略在抗癌治疗中的巨大前景。
Abstract Cellular senescence is traditionally considered as stable cell cycle arrest state with other phenotypic alterations including the production of an array of cytokines and growth factors. Cancer cells undergo senescence in response to chemotherapeutic agents, radiotherapy and molecular targeted therapy. This form of senescence is termed therapy-induced senescence (TIS) and represents a desirable target in cancer therapy. Recent studies have shown that cellular senescence is a highly heterogeneous and dynamic process. Apart from being cleared by the immune system, the senescent cancer cells may survive for a long time and escape from senescence state. Notably, these cells even have the potential to regain stem-like state with high aggressiveness that eventually facilitates cancer recurrence. Furthermore, the senescence-associated secretory phenotype (SASP) of senescent cells is not always the same, and could establish immunosuppression and a protumor microenvironment. Given these detrimental effects, senescence-inducing chemotherapy followed by senotherapy (the “one–two punch” approach), has emerged. This combined therapy could mitigate unnecessary side effects of the persistent senescent cells, reduce the toxicity of pro-senescence therapy and prolong the survival of cancer patients, and it has a potential future in the precise treatment of cancer. Herein, we review the complex effects of therapy-induced senescence in cancer and highlight the great promise of two-step strategies in anticancer therapies.