Herceptin: mechanisms of action and resistance

Cancer Lett. 2006 Feb 8;232(2):123-38. doi: 10.1016/j.canlet.2005.01.041.


HER-2 is overexpressed in 20-25% of invasive breast cancers and is associated with an aggressive tumor phenotype and reduced survival rate. The HER-2 status of a tumor is the critical determinant of response to the HER-2-targeted antibody Herceptin. Thus, accurate assessment of HER-2 expression levels is essential for identifying breast cancer patients who will benefit from HER-2-targeted therapy. Herceptin combined with chemotherapy increases response rates, time to disease progression, and survival. However, the majority of cancers that initially respond to Herceptin begin to progress again within 1 year. This review describes mechanisms by which Herceptin inhibits cell growth in breast cancers that overexpress HER-2 and highlights possible mechanisms contributing to Herceptin resistance.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Clinical Trials as Topic
  • Cyclin-Dependent Kinase Inhibitor p27 / physiology
  • DNA Repair / drug effects
  • Drug Resistance, Neoplasm
  • Humans
  • Receptor, ErbB-2 / analysis
  • Signal Transduction / drug effects
  • Trastuzumab


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p27
  • Receptor, ErbB-2
  • Trastuzumab