Fig. 2.
Key examples of therapy‐induced SASP. Many cancer therapy modalities induce senescence and associated SASP, and these can influence treatment efficacy in various ways. Chemotherapy (purple box): Nacarelli et al. (2020) showed that platinum‐based chemotherapy induces cellular senescence, which can promote the formation of cancer stem cells, eventually promoting tumour relapse [9]. Treatment with the NAMPT inhibitor FK866 suppressed these cancer stem cells, preventing outgrowth of cisplatin‐treated epithelial ovarian cancer cells. Radiation (green box): Laberge et al. (2015) showed that rapamycin (an mTOR inhibitor) prevented NFκB‐driven pro‐inflammatory SASP that is induced by radiation treatment of prostate cancer cells and fibroblasts, therefore inhibiting tumour progression [36]. Immunotherapy (blue box): Däbritz et al. (2016) used a CD20‐targeting monoclonal antibody to sensitise B‐cell lymphoma cells to senescence induction alongside chemotherapy [60]. This resulted in reinforcement of senescence and enhancement of immune cell action [60]. Targeted therapy (yellow box): Guan et al. (2017) showed that prolonged exposure to palbociclib, a CDK4/6 inhibitor (CDK4/6i), could induce senescence in normal fibroblasts in a DNA damage‐independent mechanism [53]. These fibroblasts exhibited MDM2 destabilisation and sustained p21Cip1/Waf1 expression, which resulted in the promotion of melanoma growth and enhanced immunosuppression [53].