Inhibition of ATP binding cassette transporter B1 sensitizes human hair follicles to chemotherapy-induced damage

Hair follicles (HFs) are sensitive to xenobiotic damage, which can ultimately lead to hair loss such as in chemotherapy-induced alopecia (CIA) [ [1] Paus R. Haslam I.S. Sharov A.A. Botchkarev V.A. Pathobiology of chemotherapy-induced hair loss. Lancet Oncol. 2013; 14: e50-9 Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar ]. Members of the ATP-binding cassette (ABC) transporter family fulfil a crucial role in xenobiotic handling, where they actively extrude drugs thereby reducing intracellular drug accumulation and limiting cellular toxicity [ [2] Robey R.W. Pluchino K.M. Hall M.D. Fojo A.T. Bates S.E. Gottesman M.M. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat. Rev. Cancer. 2018; : 1 Google Scholar ]. Recently, we demonstrated that human scalp hair follicles (HFs) express an array of ABC transporter proteins, many of which localise to the anagen hair matrix (HM) and the bulge [ [3] Haslam I.S. El-Chami C. Faruqi H. Shahmalak A. O’Neill C.A. Paus R. Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle. Br. J. Dermatol. 2015; 172: 1562-1572 Crossref PubMed Scopus (22) Google Scholar ]. One predicted, but as yet unproven role for these ABC transporters may be to protect defined HF cell populations against chemotherapy-induced damage and thus provide a novel solution to this unmet clinical problem [ [3] Haslam I.S. El-Chami C. Faruqi H. Shahmalak A. O’Neill C.A. Paus R. Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle. Br. J. Dermatol. 2015; 172: 1562-1572 Crossref PubMed Scopus (22) Google Scholar , [4] Haslam I.S. Pitre A. Schuetz J.D. Paus R. Protection against chemotherapy-induced alopecia: targeting ATP-binding cassette transporters in the hair follicle?. Trends Pharmacol. Sci. 2013; 34: 599-604 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ]. Although the physiological role for these transporters in human HF biology remains largely elusive, dye exclusion assays suggest that ABCB1, ABCG2 and ABCC1 can reduce substrate accumulation in key regions of the human HF epithelium [ [3] Haslam I.S. El-Chami C. Faruqi H. Shahmalak A. O’Neill C.A. Paus R. Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle. Br. J. Dermatol. 2015; 172: 1562-1572 Crossref PubMed Scopus (22) Google Scholar ]. The current pilot study examines whether ABC transporter activity in the human HF impacts on the cytotoxicity of anticancer drugs known to cause extensive hair loss [ [1] Paus R. Haslam I.S. Sharov A.A. Botchkarev V.A. Pathobiology of chemotherapy-induced hair loss. Lancet Oncol. 2013; 14: e50-9 Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar ].