Hedgehog Pathway Inhibitors

The Hedgehog (Hh) signaling pathway is integral in a number of physiologic processes including fetal development, tissue patterning, maintenance of stem cell populations, and regulation of hair follicles. It is also involved in the pathogenesis of a variety of neoplasms. As such, it has been targeted in the treatment of a variety of malignancies that most recently includes basal cell carcinoma (BCC). Vismodegib is a first-in-class agent selectively targeting the Hh signaling pathway for treatment of patients with locally advanced and metastatic BCC. Sonidegib was subsequently approved with several additional Hh pathway inhibitors currently under development. Hh pathway inhibition has also been studied in a number of additional dermatologic conditions including Merkel cell carcinoma and the cutaneous manifestations of graft-versus-host disease.