CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane-induced alopecia

ABSTRACT: Taxanes are a leading cause of severe and permanent chemotherapy-induced alopecia. As the underlying pathobiology of taxane chemotherapy-induced alopecia remains poorly understood, we investigated how paclitaxel and docetaxel damage human scalp hair follicles in a clinically relevant ex vivo organ culture model. Paclitaxel and docetaxel induced massive mitotic defects and apoptosis in transit amplifying hair matrix keratinocytes and within epithelial stem/progenitor cell-rich outer root sheath compartments, including within Keratin 15+ populations, thus implicating direct damage to stem/progenitor cells as an explanation for the severity of taxane chemotherapy-induced alopecia. Moreover, by administering the CDK4/6 inhibitor palbociclib, we show that transit amplifying and stem/progenitor

SUBMITTER: Dr. Talveen Purba 

PROVIDER: S-SCDT-EMM-2019-11031 | biostudies-other |

REPOSITORIES: biostudies-other