As cells with TP53 mutations lack an effective G1 checkpoint,they become over-reliant on the G2 checkpoint; therefore inhibitionof WEE1, which acts in the G2 checkpoint, is thought to cause SL.This has been demonstrated in TP53 mutant colorectal carcinoma where,after exposure to radiation, inhibition of WEE1 with the preclinicalinhibitor PD0166285 (42, Figure 13C) caused the cells to evade G2 arrest andprematurely enter mitosis.113 Furthermore, 40 has shown substantial improvement in carboplatin treatmentof advanced solid tumors with p53 mutants in phase I and phase IItrials.114,115. The gene discussed is TP53; the disease is colorectal carcinoma.