TP53 and cancer: 1. Mechanistically, many chemotherapies cause DNA damage in cancer cells, which triggers senescence through ATM–CHK2 and ATR–CHK1 kinase-mediated activation of the interconnected p53–RB pathways.2. Radiotherapy can induce an irreparable DNA damage response that activates ATM or ATR and p53–p21 pathway-mediated apoptosis and cellular senescence.3. SASP cytokines, chemokines and other factors that modulate immune cells can either promote or inhibit senescent cell clearance.