CDK4/6 Inhibition Mitigates Stem Cell Damage in a Novel Model for Taxane-Induced Alopecia

    September 2019 in “ EMBO Molecular Medicine
    Talveen S. Purba, Kayumba Ng’andu, Lars Brunken, Eleanor Smart, Ellen Sullivan Mitchell, N. M. K. Nik Hassan, Aaron O’Brien, Charlotte E. L. Mellor, Jennifer Jackson, Asim Shahmalak, Ralf Paus
    TLDR CDK4/6 inhibitors can protect hair cells from chemotherapy damage.
    The study investigated the effects of taxane chemotherapy, specifically paclitaxel and docetaxel, on human scalp hair follicles using an ex vivo organ culture model. It found that these chemotherapies caused significant mitotic defects and apoptosis in hair matrix keratinocytes and epithelial stem/progenitor cells, contributing to severe and often permanent alopecia. The CDK4/6 inhibitor palbociclib was shown to protect these cells from paclitaxel-induced cytotoxicity by inducing G1 arrest, without causing additional hair follicle damage. This highlighted the potential of epithelial stem/progenitor cell-protective therapy in mitigating taxane-induced alopecia and provided preclinical evidence that G1 arrest therapy could limit tissue damage caused by taxanes. The study involved hair follicles from 3 patients, with various analyses performed on 4-13 hair follicles per condition.
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