However, non-canonical Gli activation independent of SHh, has been shown in many cancer cells types [17, 18], and there is evidence for mechanisms of Gli activation independent of SHh, stimulated by other oncogenic signaling pathways such as transforming growth factor β (TGFβ), epidermal growth factor receptor (EGFR), RAS and AKT/PI3K pathways [19–23]. The gene discussed is GLI1; the disease is cancer.