Pathobiology of chemotherapy-induced hair loss

Institute of Inflammation and Repair, University of Manchester, Manchester, UK. Electronic address: .
The Lancet Oncology (Impact Factor: 24.69). 02/2013; 14(2):e50-e59. DOI: 10.1016/S1470-2045(12)70553-3
Source: PubMed


Hair loss can be a psychologically devastating adverse effect of chemotherapy, but satisfactory management strategies for chemotherapy-induced alopecia remain elusive. In this Review we focus on the complex pathobiology of this side-effect. We discuss the clinical features and current management approaches, then draw upon evidence from mouse models and human hair-follicle organ-culture studies to explore the main pathobiology principles and explain why chemotherapy-induced alopecia is so challenging to manage. P53-dependent apoptosis of hair-matrix keratinocytes and chemotherapy-induced hair-cycle abnormalities, driven by the dystrophic anagen or dystrophic catagen pathway, play important parts in the degree of hair-follicle damage, alopecia phenotype, and hair-regrowth pattern. Additionally, the degree of hair-follicle stem-cell damage determines whether chemotherapy-induced alopecia is reversible. We highlight the need for carefully designed preclinical research models to generate novel, clinically relevant pointers to how this condition may be overcome.

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Available from: Iain Haslam, Jan 03, 2014
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    • "The side effects and drug resistance are both believed to be consequences of the chemotherapy drugs' mechanism of action, which is mainly directed at halting cell division by damaging DNA. Side effects arise because the Pt-based drug effect is not restricted to cancer cells; it influences the normal cells that continuously proliferate as well [2] [3] [4] [5] [6]. The current study focuses on increasing the effect of CisPt at a low dose thereby enabling a lower dose to be administered, resulting in fewer side effects caused by the fact that CisPt is inherently not specific to cancer cells. "
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    • "When cell mitosis abruptly ceases as a result of cytotoxic therapy, the partially keratinized hair shaft weakens and falls out, resulting in anagen dystrophic effluvium (Ulrich et al., 2008). In addition, chemotherapeutic agents can cause p53-dependent apoptosis in the follicular epithelium resulting in premature transitioning from anagen to catagen and cause telogen effluvium (Botchkarev, 2003; Paus et al., 2013). The consequence of these processes is hair shedding, which can begin within 1 to 3 weeks and is often complete within 1 to 2 months after beginning chemotherapy (Trueb, 2009). "
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    • "Ion channels have shown to have important roles not only in cell maintenance but also in stem/progenitor cells [29]. Because cytotoxic agents damage the proliferating progenitor cells in the hair matrix [13], we suspect that several ion channels might be involved in chemotherapy-induced alopecia and be promising targets for development of novel treatments. "
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