GDC-0449--targeting the hedgehog signaling pathway.

Hedgehog signaling is activated in a variety of solid tumors and hematologic malignancies by point mutations in hedgehog pathway members or autocrine or paracrine ligand secretion. Several hedgehog inhibitors were developed to block hedgehog pathway activity on the level of the activating receptor, Smoothened (Smo). GDC-0449 is the first systemic Smo-inhibitor entering clinical trials. It was successfully tested in a phase-I clinical trial demonstrating good pharmacodynamic (PD) and pharmacokinetic (PK) properties and showing objective response and clinical benefit in several patients with basal cell carcinoma.