MDM2-PROTAC versus MDM2 Inhibitors: Beyond p53 Reactivation

Cancer Discov. 2023 May 4;13(5):1043-1045. doi: 10.1158/2159-8290.CD-23-0229.

Abstract

In this issue of Cancer Discovery, Adams and colleagues present the discovery of a potent PROTAC, MDM2 degrader, which activates wild-type p53 leading to cancer cell death. Importantly, in a number of in vitro and in vivo experiments, the authors show that the depletion of MDM2 by PROTAC kills p53-mutant or p53-null cancer cells. See related article by Adams et al., p. 1210 (5).

Publication types

  • Editorial
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Triple Negative Breast Neoplasms*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-mdm2
  • Antineoplastic Agents
  • MDM2 protein, human