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

Talveen Purba, Kayumba Ng'andu, Lars Brunken, Eleanor Lech, Ellen Mitchell, Nashat Hassan, Aaron O'Brien, Charlotte Mellor, Jennifer Jackson, Asim Shahmalak , Ralf Paus

Research output: Contribution to journalArticlepeer-review


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 cells can be protected from paclitaxel cytotoxicity through G1 arrest, without premature catagen induction and additional hair follicle damage. Thus, the current study elucidates the pathobiology of taxane chemotherapy-induced alopecia, highlights the paramount importance of epithelial stem/progenitor cell-protective therapy in taxane-based oncotherapy, and provides preclinical proof-of-principle in a healthy human (mini-) organ that G1 arrest therapy can limit taxane-induced hair follicle damage.
Original languageEnglish
JournalEMBO Molecular Medicine
Early online date12 Sept 2019
Publication statusPublished - 1 Oct 2019


  • Taxotere
  • Taxol
  • Palbociclib
  • Chemotherapy
  • Hair Loss


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