MDM2-TP53 Crossregulation: An Underestimated Target to Promote Loss of TP53 Function and Cell Survival.

Half of human cancers bear inactivating mutations of the tumor suppressor gene TP53, but the other half do not. In a recent issue of Cancer Cell, Dhar et al. and Zhu et al. reported that, in liver cancer and medulloblastoma, MDM2 is constitutively activated, causing a loss of TP53 function that does not require TP53 mutation. On theoretical grounds, such cancer would be amenable to treatment with MDM2 inhibitors.