SHH-driven cancers arise from a variety of mutations that affect different components, including the key transcriptional effector Gli proteins, leads to a variety of human malignancies including medulloblastoma, rhabdomyosarcoma, melanoma, basal cell carcinoma, and breast, lung, liver, stomach, prostate, and pancreatic cancers [16], [17], [18], [19], [20]. The gene discussed is GLI1; the disease is melanoma.