P53 is a key regulator of the G1 checkpoint and is one of the most frequently mutated genes in cancer. Therefore, a majority of human cancers lack G1checkpoint but retain the S- and G2-phase checkpoints. As a result of p53 deficiency,cells lacking the G1 checkpoint are predicted to be more dependent on the Wee1-mediated G2 checkpoint. Hence, p53-deficient tumors treated with inhibitors of Wee1 may be particularly susceptible to DNA damage because multiple checkpoints have been lost.