The roles of mutant p53 in reprogramming and inflammation in breast cancers

Abstract

Rezatapopt is an investigational small molecule p53 reactivator that binds specifically to the Y220C-mutant p53 protein without interacting with wild-type or other mutant p53 proteins. Upon binding, rezatapopt stabilizes the Y220C-mutant p53 protein in the wild-type conformation, reactivating p53 functions. The Phase 1 PYNNACLE trial assessed rezatapopt in solid tumors. One study participant with triple-negative breast cancer experiencing severe inflammation of the skin overlying the breast and left arm edema saw inflammation improve within 1 week of receiving rezatapopt and completely resolve shortly after. After 6 weeks of treatment, tumor volume had reduced 41%. The patient remains on study, with continued resolution of the skin inflammation and reduced tumor burden for greater than 24 months. There are several wild type Tp53 regulated pathways that could play a role in reversing the inflammatory response and tumor growth observed in this patient case. This perspective explores the signal transduction pathways involved in this cancer mediated inflammation and the extensive reduction of detectable tumor tissue.