Dermato-Oncology Unit, First Department of Dermatology, University of Athens, Andreas Syggros Hospital, Athens, Greece.
Br J Dermatol. 2017 Dec;177(6):1485-1494. doi: 10.1111/bjd.15738. Epub 2017 Oct 25.
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 (HPIs) vismodegib and sonidegib. In the skin, physiological Hh signalling is activated in growing hair follicles (HFs), where it is required for proliferation of the epithelium of HFs 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.
刺猬（Hh）信号通路的破译与基底细胞癌（BCC）的发生有关，这导致了靶向药物治疗的发展，即 Hh 通路抑制剂（HPIs）vismodegib 和 sonidegib。在皮肤中，生理 Hh 信号在生长的毛囊（HFs）中被激活，在形态发生过程中，它需要 HFs 的上皮细胞增殖，并在它们出生后生长。HPI 治疗导致 BCC 消退和脱发的作用，这为 Hh 通路在 BCC 形成以及毛发周期中的核心作用提供了依据。鉴于 BCC 是一种滤泡驱动的肿瘤，正是调节毛发周期的事件的微调可能导致良性滤泡错构瘤或恶性 BCC 肿瘤的形成。Wnt/β-catenin 信号在 HF 形态发生、正常毛发周期和 BCC 发育过程中与 Hh 信号相互作用。本综述的目的是展示 Hh 通路相互作用中涉及的关键分子事件如何也参与 BCC 的发病机制，并导致 HPI 治疗引起的脱发。
