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
    • "The newly forming club hair is located a short distance above the condensed DP (Figure 1f and g, feature #6). A significant portion (76.4%) of HFs-XG undergo " dystrophic catagen " (Paus et al., 2013), during which a normal, serrated club hair shaft fails to form. In addition, the regressing hair matrix above the DP commonly contains ectopic melanin deposits (Supplementary Figures S1aee and S3 online). "
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    ABSTRACT: Hair follicles (HFs) undergo life-long cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Since HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. While available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. Here, we present such a guide, which uses objective, well-defined, and reproducible criteria and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in sub-optimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field.Journal of Investigative Dermatology accepted article preview online, 09 September 2015. doi:10.1038/jid.2015.354.
    No preview · Article · Sep 2015 · Journal of Investigative Dermatology
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    • "As much as 47e58% of female patients consider hair loss to be the most traumatic aspect of chemotherapy and 8% would decline chemotherapy due to fears of hair loss [8] [9]. Therefore, the pursuit of more efficient management strategies for CIA remains a major research challenge in clinical oncology [10]. Korean Red Ginseng (KRG; the steamed root of Panax ginseng Meyer) has been an established traditional herbal medicine for > 2,000 y [11]. "
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    ABSTRACT: Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo.
    Preview · Article · Jul 2015 · Journal of ginseng research
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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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    ABSTRACT: Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death).
    Full-text · Article · Oct 2014 · BioMed Research International
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