Abnormal activation of the Sonic hedgehog (SHH) pathway has been described in a wide variety of human cancers and in cancer stem cells, such as glioblastoma stem cells, CD34+ leukemic cells and breast CSCs.
Activation of the hedgehog pathway has been implicated in the development of cancers in various organs, including brain, lung, mammary gland, prostate and skin. Basal cell carcinoma, the most common form of cancerous malignancy, has the closest association with hedgehog signaling. Loss-of-function mutations in Patched and activating mutations in Smoothened have been identified in patients with this disease. Abnormal activation of the pathway probably leads to development of disease through transformation of adult stem cells into cancer stem cells that give rise to the tumor. Cancer researchers hope that specific inhibitors of hedgehog signaling will provide an efficient therapy for a wide range of malignancies.