Cellular senescence: a double-edged sword in cancer therapy

Frontiers in Oncology

Oncology

Xing-Zhen Chen¹  Shuai Xiao²  Xueyang Hou²  Hao Lyu²  Dongmin Qin²  Cefan Zhou²  Jingfeng Tang²  Yeping Yu²  Lingli Tian²  Dong Guo²  Rui Zhang³ 

[1] Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada;National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, China;National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, China;Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China;

关键词: cellular senescence;    cell cycle arrest;    SASP;    cancer therapy;    senotherapy;   

DOI  :  10.3389/fonc.2023.1189015

 received in 2023-03-18, accepted in 2023-08-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Over the past few decades, cellular senescence has been identified in cancer patients undergoing chemotherapy and radiotherapy. Senescent cells are generally characterized by permanent cell cycle arrest as a response to endogenous and exogenous stresses. In addition to exiting the cell cycle process, cellular senescence also triggers profound phenotypic changes such as senescence-associated secretory phenotype (SASP), autophagy modulation, or metabolic reprograming. Consequently, cellular senescence is often considered as a tumor-suppressive mechanism that permanently arrests cells at risk of malignant transformation. However, accumulating evidence shows that therapy-induced senescence can promote epithelial-mesenchymal transition and tumorigenesis in neighboring cells, as well as re-entry into the cell cycle and activation of cancer stem cells, thereby promoting cancer cell survival. Therefore, it is particularly important to rapidly eliminate therapy-induced senescent cells in patients with cancer. Here we review the hallmarks of cellular senescence and the relationship between cellular senescence and cancer. We also discuss several pathways to induce senescence in tumor therapy, as well as strategies to eliminate senescent cells after cancer treatment. We believe that exploiting the intersection between cellular senescence and tumor cells is an important means to defeat tumors.

【 授权许可】

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Copyright © 2023 Xiao, Qin, Hou, Tian, Yu, Zhang, Lyu, Guo, Chen, Zhou and Tang