Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells.

ABSTRACT: The protein p53 protects the organism against carcinogenic events by the induction of cell cycle arrest and DNA repair program upon DNA damage. Virtually all cancers inactivate p53 either by mutations/deletions of the TP53 gene or by boosting negative regulation of p53 activity. The overexpression of MDM2 protein is one of the most common mechanisms utilized by p53^wt cancers to keep p53 inactive. Inhibition of MDM2 action by its antagonists has proved its anticancer potential in vitro and is now tested in clinical trials. However, the prolonged treatment of p53^wt cells with MDM2 antagonists leads to the development of secondary resistance, as shown first for Nutlin-3a, and later for three other small molecules. In the present study, we show that secondary resis

SUBMITTER: Skalniak L 

PROVIDER: S-EPMC6266412 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature