The GLI genes, GLI1 and GLI2, are are zinc finger transcription factors that regulate target genes at the distal end of the canonical Hedgehog (HH) signaling pathway (SHH- > PTCH- > SMO- > GLI). They play a role in normal cellular processes of embryogenesis, tissue patterning, and differentiation. Being oncogenes, both  GLI1 and GLI2 can induce transformation and tumorigenesis, and are constitutively activated in many types of human cancers. Oncogenic pathways, including KRAS/BRAF that occur in high frequency in colon cancer, circumvent the canonical HH-GLI axis by converging on and further driving GLI to a higher activating state in tumor cells, promoting cellular proliferation, tumor progression and survival[1].