ADAM10 as a target for anti-cancer therapy

Curr Pharm Biotechnol. 2008 Feb;9(1):2-8. doi: 10.2174/138920108783497613.

Abstract

There is a great unmet medical need in the area of cancer treatment. A potential therapeutic target for intervention in cancer is ADAM10. ADAM10 is a disintegrin-metalloproteinase that processes membrane bound proteins from the cell surface to yield soluble forms. Pharmaceutical companies are actively seeking out inhibitors of ADAM10 for treatments in cancer as the enzyme is known to release the ErbB receptor, HER2/ErbB2 from the cell membrane, an event that is necessary for HER2 positive tumor cells to proliferate. ADAM10 is also capable of processing betacellulin indicating that an inhibitor could be used against EGFR/ErbB1 and/or HER4/ErbB4 receptor positive tumor cells that are betacellulin-dependent. ADAM10 is the principle sheddase for several other molecules associated with cancer proliferation, differentiation, adhesion and migration such as Notch, E-cadherin, CD44 and L1 adhesion molecule indicating that targeting ADAM10 with specific inhibitors could be beneficial.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADAM Proteins / antagonists & inhibitors
  • ADAM Proteins / metabolism*
  • ADAM10 Protein
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism*
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Drug Delivery Systems / methods*
  • Humans
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Protease Inhibitors / administration & dosage

Substances

  • Antineoplastic Agents
  • Membrane Proteins
  • Protease Inhibitors
  • Amyloid Precursor Protein Secretases
  • ADAM Proteins
  • ADAM10 Protein
  • ADAM10 protein, human