549 Temporary cell cycle arrest in human scalp hair follicles and their epithelial stem cells by ALRN-6924: A novel strategy to selectively protect p53-wildtype cells against paclitaxel-induced alopecia

Abstract

Chemotherapy-induced alopecia (CIA) is a highly distressing side effect of cancer therapy, and taxanes like paclitaxel (PTX) cause severe and often permanent CIA. Yet, strategies that selectively protect healthy cells, but not cancer cells, remain elusive. Here, we turned to ALRN-6924, a new clinical-stage MDM2/MDMX dual inhibitor that activates p53 to upregulate p21 and thus transiently arrests cell cycle in p53-wild-type healthy cells, but not p53-mutated cancer cells. Indeed, ALRN-6924 protects human fibroblasts (HS68) from multiple chemotherapies in vitro, but not p53-mutant breast cancer cells (BT-474).