PI3K inhibition overcomes trastuzumab resistance: blockade of ErbB2/ErbB3 is not always enough

Cancer Cell. 2009 May 5;15(5):353-5. doi: 10.1016/j.ccr.2009.04.004.

Abstract

Trastuzumab targets ErbB2 and is used for treating ErbB2-overexpressing breast cancers. In this issue of Cancer Cell, Junttila et al. show that trastuzumab disrupts ligand-independent ErbB2/ErbB3/PI3K complexes and blocks AKT signaling; if PI3K is mutated, complex disruption does not inhibit AKT, which explains why trastuzumab is ineffective in some tumors.

Publication types

  • Comment

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Humans
  • Mutation
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphoinositide-3 Kinase Inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-3 / antagonists & inhibitors
  • Receptor, ErbB-3 / metabolism
  • Signal Transduction / drug effects
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Proto-Oncogene Proteins c-akt
  • Trastuzumab