ADAM10 as a therapeutic target for cancer and inflammation

Howard C. Crawford, Peter J. Dempsey, Gordon Brown, Liana Adam, Marcia L. Moss

Research output: Contribution to journalReview article

65 Scopus citations

Abstract

Both cancer and chronic inflammatory diseases are often marked by homeostatic signal transduction pathways run amok. Cleavage of membrane-bound substrates by extracellular metalloproteinases is frequently the rate limiting step in activating many of these pathways, resulting either in liberation of active ligands (shedding) or initiating further processing into bioactive cytoplasmic domains (regulated intramembrane proteolysis or RIP). ADAM10 is a member of the ADAM (A Disintegrin And Metalloproteinase) family of transmembrane metalloproteinases implicated in the RIPing and shedding of dozens of substrates that drive cancer progression and inflammatory disease, including Notch, E-cadherin, EGF, ErbB2 and inflammatory cytokines. ADAM10's emerging role as a significant contributor to these pathologies has led to intense interest in it as a potential drug target for disease treatment. Here we discuss some of the established functions of ADAM10 and the implications of its inhibition in disease progression.

Original languageEnglish (US)
Pages (from-to)2288-2299
Number of pages12
JournalCurrent pharmaceutical design
Volume15
Issue number20
DOIs
StatePublished - Aug 31 2009

Keywords

  • ADAM10
  • CD23
  • CD44
  • Cancer
  • Chemokine
  • Disintegrin
  • E-cadherin
  • ErbB
  • FasL
  • Inflammation
  • Inhibition
  • Metalloproteinase
  • Notch
  • Signaling
  • TNFα

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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  • Cite this

    Crawford, H. C., Dempsey, P. J., Brown, G., Adam, L., & Moss, M. L. (2009). ADAM10 as a therapeutic target for cancer and inflammation. Current pharmaceutical design, 15(20), 2288-2299. https://doi.org/10.2174/138161209788682442