Among the p53-activating small molecules in clinical trials for CRC (Figure 1), Idasanutlin (1, NCT03555149), Siremadlin (2, NCT03714958), and CGM097 (3, NCT01760525) effectiveness is limited only to wild-type (wt) p53 expressing CRC, and small molecule COTI-2 (4, NCT02433626) is a mutant p53 activator which mechanism of action results still unclear [21,22]. The gene discussed is TP53; the disease is colorectal carcinoma.