DNER and neoplasm: A working model was also illustrated based on our findings (Fig. 7H), in which, after a first-line therapy (targeting YAP1 or using chemotherapeutic agents or the BET inhibitor), the damaged DNA will dictate cells to undergo senescence; at the second-line therapy, directly targeting p21 expression or using the senolytic agent ABT263 is essential for triggering senescent cells to undergo apoptosis in patients with compromised immune systems that are incapable of clearing senescent cells from the tumor microenvironment.