Taxane Chemotherapy Induces Epigenetic Changes and Premature Senescence in Human Scalp Hair Follicles

This study investigates the effects of taxane chemotherapy, specifically paclitaxel, on human scalp hair follicles (HFs) and its role in chemotherapy-induced alopecia (CIA). Using organ-cultured HFs from 3 donors, the research found that paclitaxel treatment led to significant declines in nuclear Lamin B1, SIRT1, and PGC1α, indicating premature HF senescence. Additionally, there was a reduction in DNA methylation markers and an increase in DNA demethylation markers, suggesting DNA hypomethylation. Paclitaxel-treated HFs also exhibited increased DNA damage. These findings suggest that taxanes not only cause direct DNA damage and premature senescence in HFs but also induce epigenetic changes that impair HF regeneration, potentially leading to permanent CIA. Addressing these mechanisms is crucial for preventing permanent CIA.