Hedgehog signaling pathway inhibitors in the treatment of basal cell carcinoma: An Updated Review

Basal cell carcinoma (BCC) is the most common type of skin cancer that usually appears in sun-exposed body regions such as the head, trunk, and extremities. There are four main clinicopathological subtypes of BCC: nodular, superficial, morpheaform, and fibroepithelial. BCC's molecular basis includes inherited genetic susceptibility and somatic mutations, often induced by exposure to UV radiation. The aberrant activation of the Hedgehog (Hh) signaling pathway, caused by mutations in the Hh components, plays a central role in the molecular pathogenesis of this carcinoma. This led to the development of Hh signaling pathway inhibitors as a new treatment option for patients with advanced disease. In this review, we summarize BCC's clinical presentation and histopathology and present knowledge on the most studied Hh signaling inhibitors, vismodegib and sonidegib, and other inhibitors of this signaling, such as itraconazole, patidegib, taladegib, and arsenic trioxide, in the treatment of BCC. We also present the most common Hh signaling inhibitor adverse events and their management options, which could improve patients' quality of life during treatment.