Targeting Hedgehog - A cancer stem cell pathway

Akil A. Merchant, William Matsui

Research output: Contribution to journalArticlepeer-review

352 Scopus citations


The Hedgehog (Hh) pathway has been implicated in a wide variety of human tumors, and early clinical trials with pathway antagonists have validated Hh signaling as a bona fide anticancer target. Despite these encouraging results, several issues surrounding the basic biology of the Hh pathway in human cancers remain unclear. These include the influence of specific oncogenic events on Hh signal transduction, the precise mode of Hh signaling (i.e., autocrine or paracrine) that occurs within human tumors, and the best means to inhibit aberrant pathway activity in the clinical setting. The cancer stem cell (CSC) hypothesis may explain a number of clinical phenomena, such as unchecked self-renewal and the development of metastatic disease, and to some extent, the Hh signaling pathway has been implicated in all of these processes. Therefore, Hh pathway inhibitors may also represent some of the first agents to formally examine the CSC hypothesis in the clinical setting. The diverse nature of Hh signaling in human cancers suggests that disease-specific factors must be carefully considered to identify the optimal use of novel pathway inhibitors.

Original languageEnglish (US)
Pages (from-to)3130-3140
Number of pages11
JournalClinical Cancer Research
Issue number12
StatePublished - Jun 15 2010

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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