From Basal Cell Carcinoma Morphogenesis to Alopecia Induced by Hedgehog Inhibitors: Connecting the Dots

The review article by Dessinioti et al. from 2017 connects the molecular mechanisms of hair follicle development and the pathogenesis of basal cell carcinoma (BCC), focusing on the hedgehog (Hh) signaling pathway and its interaction with Wnt/ß-catenin signaling. The Hh pathway is essential for hair follicle development and cycling but is also aberrantly activated in BCC. The use of Hh pathway inhibitors (HPIs) like vismodegib and sonidegib for treating advanced BCC can lead to tumor regression but also cause alopecia, with 15% to 60% of patients affected, and higher rates with vismodegib. The alopecia is due to the inhibition of the transition of hair follicles to the anagen phase. The review suggests that while alopecia is a significant side effect, it should not deter HPI treatment, although its management lacks systematic study. It also notes that selective HPIs that spare normal hair follicles could prevent alopecia and that overexpression of Shh in mice has been shown to accelerate hair growth, hinting at potential hair loss therapies.