New prospects for drug development: The hedgehog pathway revealed. Focus on hematologic malignancies

Agustin Pimentel, Michel Velez, Luz J. Barahona, Ronan Swords, Lazaros Lekakis

Research output: Contribution to journalReview article

6 Scopus citations

Abstract

The hedgehog (Hh) pathway is a critical regulator of vertebrate embryonic development and is involved in the function of processes such as stem cell maintenance and differentiation, tissue polarity and cell proliferation. Given how critical these functions are, it is not surprising that mutations in Hh pathway components are often implicated in the tumorigenesis of a variety of human cancers. Promotion of tumor growth has recently been shown by activated Hh signaling in the tumor itself, as well as by pathway activation within surrounding cells comprising the tumor microenvironment. Targeted disruption of various Hh pathway proteins has been successfully employed as an anticancer strategy with several synthetic Hh antagonists now available. Here, the molecular basis of Hh signaling, the therapeutic rationales for targeting this pathway and the current status of Hh pathway inhibitors in the clinic are reviewed.

Original languageEnglish (US)
Pages (from-to)681-697
Number of pages17
JournalFuture Oncology
Volume9
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • Gli
  • hedgehog
  • leukemia
  • lymphoma
  • myeloma
  • smoothened

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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