The determinants of sensitivity and mechanism of action of eprenetapopt (APR-246)

Abstract

The tumour suppressor gene TP53 is mutated in over half of all cancers, resulting in mutant p53 protein accumulation and poor patient survival. Decades after the discovery that p53 plays a central role in the human body’s defence against cancer, the development of effective therapeutic strategies to target mutant p53 cancers still remains an unmet need in oncology. Eprenetapopt (also known as APR-246 and PRIMA-1MET) is currently in clinical development as a mutant p53 reactivator. The reported mechanism of action of eprenetapopt is to restore wild-type p53 functionality to mutant p53 in cancer cells, triggering p53-dependent cell cycle arrest and caspase- dependent apoptosis. As a result, cl..