Combination therapy with p53–MDM2 binding inhibitors for malignancies

Abstract

p53 is a powerful tumor suppressor, and p53–MDM2 protein–protein interaction has been considered as an attractive cancer therapeutic target. More recently developed small molecules exert their effects by interrupting the p53–MDM2 binding and enhancing the anti-proliferative activities of p53. Small molecules such as Nutlin, MI-63, MI-219, and MI-319 that can activate p53 have shown their anti-tumor effects in different types of malignancies. Drug combinations between p53–MDM2 binding inhibitors with the other anti-proliferative small molecules may allow reduction in the amount of single component with a lower incidence of side effects or better therapeutic effects. In this current review, we present the recent achievements in combination applications between p53–MDM2 binding inhibitors with other small molecules in malignancies. In addition, we discuss how this combination holds promise as a therapeutic strategy for recent and future novel therapies in these diseases.