Low-Intensity Ultrasound as a Potential Intervention Strategy to Protect Human Scalp Hair Follicles from Taxane-Induced Toxicity

Taxanes, such as paclitaxel (PTX) and docetaxel, are highly effective antimicrotubule agents frequently used in cancer therapy ( Ciccarese et al., 2022 Ciccarese C. Iacovelli R. Sternberg C.N. Gillessen S. Tortora G. Fizazi K. Triplet therapy with androgen deprivation, docetaxel, and androgen receptor signalling inhibitors in metastatic castration-sensitive prostate cancer: A meta-analysis. Eur J Cancer. 2022; 173: 276-284 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar ; Li et al., 2022 Li N. Wu T. Hong Y.G. Guo Y.Z. Cheng Y.F. Ma Y.J. et al. A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma. BMC Med. 2022; 20: 472 Crossref PubMed Scopus (1) Google Scholar ; Liu et al., 2022 Liu J. Wang P. Huang B. Cheng Q. Duan Y. Chen L. et al. Effective suppression of triple negative breast cancer by paclitaxel nanoparticles conjugated with transmembrane TNF-α monoclonal antibody. Int J Pharm. 2022; 624121969 Crossref Scopus (4) Google Scholar ; Smith et al., 2022 Smith E.R. Huang M. Schlumbrecht M.P. George S.H.L. Xu X.X. Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy - non-mitotic mechanisms of paclitaxel. Front Oncol. 2022; 12907520 Crossref Scopus (2) Google Scholar ). Taxanes target tubulin and stabilize microtubule filaments, thus altering their dynamics and resulting in cell cycle arrest and death ( Ahmed Khalil et al., 2022 Ahmed Khalil A. Rauf A. Alhumaydhi F.A. Aljohani A.S.M. Javed M.S. Khan M.A. et al. Recent Developments and Anticancer Therapeutics of paclitaxel: an update. Curr Pharm Des. 2022; 28: 3363-3373 Crossref PubMed Scopus (2) Google Scholar ; Christensen, 2022 Christensen S.B. Drugs that changed society: microtubule-targeting agents belonging to Taxanoids, macrolides and non-ribosomal peptides. Molecules. 2022; 27: 5648 Crossref PubMed Scopus (4) Google Scholar ; Smith and Xu, 2021 Smith E.R. Xu X.X. Breaking malignant nuclei as a non-mitotic mechanism of Taxol/paclitaxel. J Cancer Biol. 2021; 2: 86-93 PubMed Google Scholar ). Unsurprisingly, taxanes have major dose-limiting adverse effects, which include significant hair loss in up to 87% of patients ( Trüeb, 2009 Trüeb R.M. Chemotherapy-induced alopecia. Semin Cutan Med Surg. 2009; 28: 11-14 Crossref PubMed Scopus (125) Google Scholar ). This taxane-induced alopecia can be permanent in >10% of PTX-treated and 23% of docetaxel-treated patients ( Chan et al., 2021 Chan J. Adderley H. Alameddine M. Armstrong A. Arundell D. Fox R. et al. Permanent hair loss associated with taxane chemotherapy use in breast cancer: a retrospective survey at two tertiary UK cancer centres. Eur J Cancer Care (Engl). 2021; 30e13395 Crossref Scopus (13) Google Scholar ; Freites-Martinez et al., 2019b Freites-Martinez A. Shapiro J. Goldfarb S. Nangia J. Jimenez J.J. Paus R. et al. Hair disorders in patients with cancer. J Am Acad Dermatol. 2019; 80: 1179-1196 Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar ), likely owing to irreversible damage to epithelial hair follicle (HF) stem cells ( Purba et al., 2019 Purba T.S. Ng’andu K. Brunken L. Smart E. Mitchell E. Hassan N. et al. CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane-induced alopecia. EMBO Mol Med. 2019; 11e11031 Crossref PubMed Scopus (30) Google Scholar ).