The proof-of-concept of restoration of wt p53 tumor-suppressive function has been demonstrated in a series of elegant papers, using multiple mouse models with conditional p53 expression.35, 36, 37 As Mdm2 and Mdmx are the key inhibitors of p53, cancers in which either or both Mdm proteins are deregulated opens an attractive opportunity to restore p53 activity by targeting either one or both inhibitors. The gene discussed is TP53; the disease is cancer.