Hitting pause on chemotherapy-induced alopecia: transient p53 activation as a guardian of the hair follicle.

Abstract

Chemotherapy-induced alopecia (CIA) is a common and highly visible adverse effect of chemotherapy with substantial psychosocial and quality-of-life burdens. In this issue, Gherardini and colleagues described a targeted strategy to prevent CIA using ALRN-6924, a stapled peptide that transiently activates p53 and induces cell cycle arrest in proliferating TP53 wild-type tissues, such as the hair follicle. In ex vivo human scalp hair follicle culture, ALRN-6924 protected matrix keratinocytes and bulge stem cells from paclitaxel- and cyclophosphamide-induced injury, reducing apoptosis, DNA damage, and other pathologic features. These findings nominate precision chemoprotection as a promising supportive care approach for mitigating CIA.