Hitting pause on chemotherapy-induced alopecia: transient p53 activation as a guardian of the hair follicle
Edward B. Li, Meredith Klay, Rui Yi
Edward B. Li, Meredith Klay, Rui Yi
View: Text | PDF
Commentary

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.

Authors

Edward B. Li, Meredith Klay, Rui Yi

×

Figure 1

Protecting the hair follicle from chemotherapy-induced injury.

Options: View larger image (or click on image) Download as PowerPoint
Protecting the hair follicle from chemotherapy-induced injury. (A) Chemo...
(A) Chemotherapy-induced alopecia (CIA) is a highly visible adverse effect of systemic chemotherapies that is often distressing to patients. The hair follicle’s vulnerability to chemotherapy is attributed to the rapid proliferation of keratinocytes in the hair follicle bulb that occurs during the anagen phase of hair growth. Chemotherapy can also damage quiescent stem cells in the epithelial hair follicle stem cell (eHFSC) bulge, which may underlie persistent CIA. (B) Gherardini et al. (9) showed that pretreating ex vivo human hair follicles with ALRN-6924 protected hair follicles from CIA. Mechanistically, ALRN-6924 reactivated p53/p21 signaling, forcing a transient cell cycle arrest that reduced apoptosis and DNA damage in bulb keratinocytes and the eHFSC compartment. This strategy highlights the potential to develop precision chemoprotective treatments as supportive care approaches to prevent CIA.