Dr. Sekulic on the Hedgehog Pathway Inhibitor Vismodegib

Aleksandar Sekulic, MD, PhD, Assistant Professor of Dermatology, Mayo Clinic, Scottsdale, AZ, discusses the Hedgehog pathway inhibitor vismodegib (Erivedge), which is approved for patients with basal cell carcinoma (BCC) and is under investigation in multiple other tumor types.

Vismodegib is an active inhibitor of the smoothened receptor, which is a key link in the Hedgehog signaling pathway. Overall, smoothened is implicated in greater than 90% of patients with BCC that have an activated Hedgehog pathway. Sekulic believes this makes it a successful target in a broad spectrum of patients.

In addition to vismodegib's activity in malignant cells it will also bind to smoothened in normal small compartment cells, such as hair follicles and taste buds. This inhibition in the noncancerous cells explains some of the adverse events of the drug, which includes altered taste and hair loss.