Drugging the cancer stem cell compartment: Lessons learned from the hedgehog andwnt signal transduction pathways

Michael E. Dodge, Lawrence Lum

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Cell-cell communication mediated by the secreted Hedgehog (Hh) and Wnt signaling molecules is essential to the coordination of cell fate decision making throughout the metazoan lifespan. From decades of genetically based interrogation, core components constituting the Hh and Wnt signal transduction pathways have been assembled, and a deep appreciation of how these signals elaborate distinct bodily tissues during development has been established. On the other hand, our incapacity to leverage similar genetic approaches to study adult organ systems has limited our understanding of how these molecules promote tissue renewal and regeneration through stem cell regulation. We discuss recent progress in the use of chemically based approaches to achieve control of these pathway activities in a broad range of biological studies and therapeutic contexts. In particular, we discuss the unique experimental opportunities that chemical modulators of these pathways afford in exploring the cancer stem cell hypothesis.

Original languageEnglish (US)
Pages (from-to)289-310
Number of pages22
JournalAnnual review of pharmacology and toxicology
Volume51
DOIs
StatePublished - Feb 10 2011

Keywords

  • Porcupine
  • Smoothened
  • Tankyrase
  • cancer therapeutics

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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