Inhibition of Hedgehog signaling in the gastrointestinal tract: Targeting the cancer microenvironment

Juanita L. Merchant, Milena Saqui-Salces

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

This review summarizes emerging information regarding the Hedgehog (Hh) signaling pathway during neoplastic transformation in the gastrointestinal tract. Although there is a role for the well-established canonical pathway in which Hedgehog ligands interact with their receptor Patched, there is sufficient evidence that downstream components of the Hh pathway, e.g., Gli1, are hijacked by non-Hh signaling pathways to promote the conversion of the epithelium to dysplasia and carcinoma. We review the canonical pathway and involvement of primary cilia, and then focus on current evidence for Hh signaling in luminal bowel cancers as well as accessory organs, i.e., liver, pancreas and biliary ducts. We conclude that targeting the Hh pathway with small molecules, nutriceuticals and other mechanisms will likely require a combination of inhibitors that target Gli transcription factors in addition to canonical modulators such as Smoothened.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalCancer Treatment Reviews
Volume40
Issue number1
DOIs
StatePublished - Feb 2014

Keywords

  • Gli1
  • MDSCs
  • Primary cilia
  • Stomach
  • Stroma

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