Mechanism of action of trastuzumab and scientific update

Semin Oncol. 2001 Oct;28(5 Suppl 16):4-11. doi: 10.1016/s0093-7754(01)90276-3.

Abstract

The humanized anti-p185(HER2) monoclonal antibody trastuzumab has been shown to effectively inhibit the growth of HER2-overexpressing breast cancer cells in vivo and in vitro. The treatment of cancer cells with trastuzumab results in downregulation of the HER2 receptor. Further downstream cellular events include the accumulation of the cyclin-dependent kinase inhibitor p27 and cell cycle arrest. In vivo, trastuzumab induces antibody-dependent cellular cytotoxicity. Trastuzumab also inhibits constitutive HER2 cleavage/shedding mediated by metalloproteases. The ability of trastuzumab to inhibit HER2 cleavage may correlate with the clinical anticancer activity of the multifunctional HER2-targeting antibody.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Cycle Proteins
  • Cell Division / drug effects
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Down-Regulation
  • Enzyme Inhibitors / therapeutic use*
  • G1 Phase / drug effects
  • Humans
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Receptors, IgG
  • Trastuzumab
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Receptors, IgG
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Cyclin-Dependent Kinases
  • Trastuzumab