Novel anticancer targets: revisiting ERBB2 and discovering ERBB3.
Aberrant receptor expression or functioning of the epidermal growth factor receptor (Erbb) family plays a crucial part in the development and evolution of cancer. Inhibiting the signalling activity of individual receptors in this family has advanced the treatment of a range of human cancers. In this Review we re-evaluate the role of two important family members, ERBB2 (also known as HER2) and ERBB3 (also known as HER3), and explore the mechanisms of action and preclinical and clinical data for new therapies that target signalling through these pivotal receptors. These new therapies include tyrosine kinase inhibitors, antibody-chemotherapy conjugates, heat-shock protein inhibitors and antibodies that interfere with the formation of ERBB2-ERBB3 dimers.
Baselga
José
J
Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain. jbaselga@vhio.net
Swain
Sandra M
SM
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D019281:Dimerization; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018841:HSP90 Heat-Shock Proteins; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C485206:pertuzumab