Cellular senescence: a double-edged sword in cancer therapy

Front Oncol. 2023 Sep 12:13:1189015. doi: 10.3389/fonc.2023.1189015. eCollection 2023.

Abstract

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.

Keywords: SASP; cancer therapy; cell cycle arrest; cellular senescence; senotherapy.

Publication types

  • Review

Grants and funding

This work was supported by the National Natural Science Foundation of China (32070726, 82273970 to JT, 32270768 to CZ), Wuhan Science and Technology Project (2022020801020272 to CZ), Hubei International Science and Technology Cooperation Project (2022EHB038 to CZ). Innovation Group Project of Hubei Province (ZROT2023000075). Doctoral Start-up Foundation of Hubei University of Technology (XJ2022003901 to SX).