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From basal cell carcinoma morphogenesis to the alopecia induced by hedgehog inhibitors: connecting the dots
Author(s) -
Dessinioti C.,
Antoniou C.,
Stratigos A.J.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15738
Subject(s) - morphogenesis , vismodegib , basal cell carcinoma , hedgehog , hedgehog signaling pathway , basal cell , basal (medicine) , cancer research , medicine , dermatology , microbiology and biotechnology , biology , pathology , genetics , signal transduction , gene , insulin
Summary The deciphering of the hedgehog (Hh) signalling pathway implicated in the tumorigenesis of basal cell carcinoma ( BCC ) led to the development of targeted drug therapies, the Hh pathway inhibitors ( HPI s) vismodegib and sonidegib. In the skin, physiological Hh signalling is activated in growing hair follicles ( HF s), where it is required for proliferation of the epithelium of HF s during morphogenesis and for their postnatal growth. The effects of HPI treatment leading to the regression of BCC and the development of alopecia underpin the central role of the Hh pathway in BCC formation, as well as hair cycling. Given the fact that BCC is a follicular‐driven tumour, it is a fine tuning of events that regulate hair cycling that may drive towards the formation of benign follicular hamartomas or malignant BCC neoplasms. Wnt/β‐catenin signalling interacts with the Hh signalling during HF morphogenesis, normal hair cycling and BCC development. The aim of this review is to present how key molecular events implicated in Hh pathway crosstalk in the HF are also involved in BCC pathogenesis and result in the alopecia developed by HPI treatment.