Targeting c-erbB2 and other receptors of the c-erbB family: rationale and clinical applications.
The c-erbB family of receptors includes four distinct receptors, namely c-erb B1, 2, 3 and 4 (HER1, 2, 3 and 4, respectively). Trastuzumab (T) is a recombinant humanized anti-HER2 monoclonal antibody that binds the extracellular domain of the receptor and blocks intracellular signalling. In clinical studies of T, either alone or in combination with chemotherapy, in HER2 overexpressing metastatic breast cancer patients, a significant benefit was obtained--improved response rates and survival, when T was combined with chemotherapy. Several trials of adjuvant T, either singly or in combination with chemotherapy, are in progress in early breast cancer patients. Pertuzumab defines a new class of HER2 inhibitors, "dimerization inhibitors" that block both homo- and hetero-dimerization of HER2. In preclinical studies pertuzumab is inhibitory to breast, prostate and non small cell lung cancer cell lines, both over and non overexpressing HER2. In phase I clinical trials pertuzumab has shown activity in a number of human cancers. A phase II program is in progress.
Bianco
A R
AR
Department of Molecular and Clinical Endocrinology and Oncology, University Federico II School of Medicine, Naples, Italy. bianco@unina.it
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D009367:Neoplasm Staging; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects; D018570:Risk Assessment; D016019:Survival Analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab