HER2 targeted therapy in breast cancer...beyond Herceptin.
HER2, is a member of the ErbB family of receptor tyrosine kinases, that plays a key role in the pathogenesis of breast cancer, and when overexpressed, can correlate with a particularly aggressive clinical phenotype. It is estimated in roughly 18 to 20% of breast cancer patients, there is amplification of the HER2 gene resulting in aberrant overexpression of p185HER2 protein. As such, HER2 represents an attractive therapeutic target. In this review, we explore the clinical evolution of trastuzumab, a humanized monoclonal antibody with high specificity and affinity for the HER2 extracellular domain, and additionally examine more recent efforts targeting the intracellular tyrosine kinase domain of HER2 using small molecule tyrosine kinase inhibitors.
Pal
Sumanta Kumar
SK
111-934 Factor Building, UCLA Center for the Health Sciences, UCLA Campus Mail Code 167817, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Pegram
Mark
M
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D000077341:Lapatinib; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human