Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: current status and future directions

Cancer Treat Rev. 2009 Dec;35(8):685-91. doi: 10.1016/j.ctrv.2009.08.001. Epub 2009 Sep 4.


Aberrant activation of HER2 through overexpression has been shown to play an important role in some breast cancers. Therapies against this receptor including the monoclonal antibody, trastuzumab, or the small tyrosine kinase inhibitor, lapatinib have shown to improve the prognosis of such patients. Despite overexpressing HER2, some patients do not respond to these targeted treatments or progress after a short period of time. Irreversible tyrosine kinase inhibitors have been developed to bypass several pathways that could be involved in this resistance. In vitro, these agents have been shown to be more potent and to prolong target inhibition. Clinical development of these agents is ongoing and early results are promising. This review will describe the biologic rationale that justifies the development of these agents in breast cancer focusing on the current status and future directions.

Publication types

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

MeSH terms

  • Afatinib
  • Aminoquinolines / therapeutic use
  • Aniline Compounds / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Drug Resistance, Neoplasm
  • ErbB Receptors / metabolism*
  • Female
  • Forecasting
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lapatinib
  • Morpholines / therapeutic use
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quinazolines / therapeutic use
  • Quinolines / therapeutic use
  • Trastuzumab
  • Up-Regulation


  • Aminoquinolines
  • Aniline Compounds
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Morpholines
  • Protein Kinase Inhibitors
  • Quinazolines
  • Quinolines
  • Lapatinib
  • Afatinib
  • Canertinib
  • EGFR protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • neratinib
  • Trastuzumab
  • EKB 569