Fig. 3From: New therapeutic strategies to treat human cancers expressing mutant p53 proteinsSelective killing of mutant p53 tumor cells through cell-cycle checkpoint abrogation. (a) Endogenous single strand breaks (SSBs) are repaired by SSB repair pathways that involve PARP1. If base excision repair (BER) is impaired, through the inhibition of PARP (for example by olaparib), single strand breaks become double strand breaks. In patients with HR defects, such as a BRCA mutation carrier, this damage causes the cancer cell death since PARP inhibitors induce aberrant activation of NHEJ. (b) Compared to wtp53 cells with an intact G1 checkpoint, mutp53 cancer cells lacking the p53-dependent G1 checkpoint may depend more on the G2 checkpoint to survive after DNA damage. The inhibition of Wee1 activity could lead to mitotic catastrophe and cell deathBack to article page