The role of Hedgehog signaling in BCC

BCC is the most commonly diagnosed human cancer, with approximately 1.9 million people treated for BCC in 2006.^14,15 Surgery cures most cases of BCC, but in some patients, there is progression to unresectable, locally advanced, or metastatic tumors that can become life-threatening.¹⁵ Currently, there is no standard of care for locally advanced or metastatic BCC, and the median survival time for patients with metastatic BCC is only 8 months.^15,16

BCC may be caused by mutations in components of the Hedgehog signaling pathway.¹⁷ Most BCC tumors have either inactivating mutations in PTCH1^2,3 or, less commonly, activating mutations in SMO.⁷ These mutations cause overactive Hedgehog signaling, which in BCC can result in uncontrolled proliferation of basal cells of the skin. Because advanced BCC relies on the activation of the Hedgehog pathway for growth and maintenance, blocking Hedgehog signaling may represent a novel therapeutic approach.^18-20