Inhibition of Hedgehog signaling in the gastrointestinal tract: targeting the cancer microenvironment.

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.

journal_name

Cancer Treat Rev

journal_title

Cancer treatment reviews

authors

Merchant JL,Saqui-Salces M

doi

10.1016/j.ctrv.2013.08.003

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

12-21

issue

1

eissn

0305-7372

issn

1532-1967

pii

S0305-7372(13)00168-0

journal_volume

40

pub_type

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