Pharmacologically Increasing Mdm2 Inhibits DNA Repair and Cooperates with Genotoxic Agents to Kill p53-Inactivated Ovarian Cancer Cells

Abstract excerpt

UNLABELLED: The Mdm2 oncogene is a negative regulator of the p53 tumor suppressor and recently identified inhibitor of DNA break repair. Nutlin-3 is a small-molecule inhibitor of Mdm2-p53 interaction that can induce apoptosis in cancer cells through activation of p53. Although this is a promising therapy for those cancers with wild-type p53, half of all human cancers have inactivated p53. Here, we reveal that a...