Non-canonical Hh signaling in cancer—Current understanding and future directions

Dongsheng Gu, Jingwu Xie

Research output: Contribution to journalReview article

32 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1684-1698
Number of pages15
Issue number3
StatePublished - Aug 27 2015


  • Gli
  • Hedgehog
  • Non-canonical
  • Smoothened

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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