Discovery of the connection between Hedgehog signaling and cancer

Hedgehog signaling was initially linked to cancer upon the characterization of Gorlin syndrome (also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome).^1-3,9 Gorlin syndrome is a rare hereditary disorder characterized by multiple BCCs and an increased risk of medulloblastoma.^9,10 The discovery that inherited loss-of-function mutations in the PTCH gene were the underlying cause of Gorlin syndrome first established a connection between the Hedgehog pathway and cancer.^1-3 Activation of the pathway via mutations was subsequently identified in sporadic BCC and medulloblastoma.^4,5,7,11-13