The combination of molecular and cellular approaches that are being employed will 1) provide critical new insight into the role of GLI1/GLI2 in driving cellular survival, which has never been addressed in any type of human cancer, and will answer a fundamental question in HH biology, 2) address how dysregulation of the GLI1/GLI2 axis induces DNA damage upstream of cell death or DNA repair upstream of cell survival and 3) provide a framework for the design of strategies and therapeutics specifically targeted at HH signaling via GLI1 and GLI2 in human colon carcinoma. The gene discussed is GLI2; the disease is colon carcinoma.