Non-Canonical Hh Signaling in Cancer—Current Understanding and Future Directions

• Main Authors: Dongsheng Gu, Jingwu Xie
• Format: Article
• Language: English
• Published: MDPI AG 2015-08-01
• Series: Cancers
• Subjects: hedgehog; non-canonical; smoothened; Gli
• Online Access: http://www.mdpi.com/2072-6694/7/3/0857

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.