Herceptin: mechanisms of action and resistance.
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.
Nahta
Rita
R
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
Esteva
Francisco J
FJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002986:Clinical Trials as Topic; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology; D004260:DNA Repair / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D000068878:Trastuzumab
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab