Fig. 1
From: Distinct mechanisms mediating therapy-induced cellular senescence in prostate cancer
Molecular pathways of senescence-inducing therapies of PCa. Several applied therapies including radiotherapy, chemotherapy and androgen receptor (AR) targeted therapy (androgen deprivation therapy, ADT; supraphysiological androgen level, SAL; AR antagonists). Radiotherapy and chemotherapy lead to persistent DNA damage which triggers ATM or ATR signaling and finally p53 and p21WAF1/CIP1 activation. p21WAF1/CIP1 inhibits CDKs and mediates senescence through hypophosphorylation of pRb. In addition, chemotherapy induces senescence through ROS-ERK-ETS-p16INK4a and the p27Kip1-pRb pathway. SAL mediates senescence by the p15INK4b-p16INK4a-pRb-E2F1 pathway. AR antagonists induce senescence through p15INK4b-p16INK4a. Senescent cells secrete many cytokines, growth factors and exosomes, known as senescence-associated secretory phenotype (SASP). These factors exert different autocrine/paracrine effects on the surrounding tumor microenvironment thereby promoting or inhibiting tumor growth (created in Biorender.com)