Non-Canonical Hh Signaling in Cancer-Current Understanding and Future Directions.
As a major regulatory pathway for embryonic development and tissue patterning, hedgehog signaling is not active in most adult tissues, but is reactivated in a number of human cancer types. A major milestone in hedgehog signaling in cancer is the Food and Drug Administration (FDA) approval of a smoothened inhibitor Vismodegib for treatment of basal cell carcinomas. Vismodegib can block ligand-mediated hedgehog signaling, but numerous additional clinical trials have failed to show significant improvements in cancer patients. Amounting evidence indicate that ligand-independent hedgehog signaling plays an essential role in cancer. Ligand-independent hedgehog signaling, also named non-canonical hedgehog signaling, generally is not sensitive to smoothened inhibitors. What we know about non-canonical hedgehog signaling in cancer, and how should we prevent its activation? In this review, we will summarize recent development of non-canonical hedgehog signaling in cancer, and will discuss potential ways to prevent this type of hedgehog signaling.
Departments of Pediatrics, Biochemistry and Molecular Biology, Pharmacology and Toxicology, The Wells Center for Pediatrics Research, 1044 W, Walnut Street, Indianapolis, IN 46202, USA. donggu@iu.edu.
Dongsheng
D
Gu
Departments of Pediatrics, Biochemistry and Molecular Biology, Pharmacology and Toxicology, The Wells Center for Pediatrics Research, 1044 W, Walnut Street, Indianapolis, IN 46202, USA. jinxie@iu.edu.
Jingwu
J
Xie
Gli; hedgehog; non-canonical; smoothened