Hedgehog-Gli signaling in basal cell carcinoma and other skin cancers: prospects for therapy

Abstract

The Hedgehog (Hh) signaling pathway is of critical importance during embryonic development, where it directs a number of cellular processes, including cell proliferation, differentiation, and patterning. In normal adult tissues, Hh signaling is mostly involved in stem cell maintenance, tissue repair, and regeneration. Over the last two decades, aberrant activation of Hh signaling has been linked to several types of cancer, including those of the skin. In particular, the critical role of Hh signaling in the development of basal cell carcinoma has been demonstrated by several mouse models and genetic mutation analyses. In addition, several clinical trials using Hh signaling inhibitors have been shown to be effective treatments in basal cell carcinoma. Recent evidence indicates that activation of the Hh pathway plays an important role in other types of human skin cancer, such as melanoma and cutaneous squamous cell carcinoma. In this review, we provide an overview of the roles of Hh pathway in skin cancers, including basal cell carcinoma, melanoma, and squamous cell carcinoma. Finally, we discuss the rapid development of drugs that target the Hh pathway and the implications for skin cancer therapy.