Growth factor receptors in breast cancer: potential for therapeutic intervention.
Increased expression and activation of receptor tyrosine kinases occurs frequently in human breast carcinomas. Several therapies targeting these receptors are currently in clinical trials. Therapeutic strategies include blockade of individual receptors with monoclonal antibodies and inhibition of tyrosine kinase function. Trastuzumab is the first of these biologic therapies to be approved for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer. Novel trastuzumab-based combinations are being investigated in patients with advanced breast cancer. Large clinical trials have also been launched in the adjuvant setting. Small molecules that inhibit specific tyrosine kinases (e.g., epidermal growth factor receptor, HER2) are in phase I and phase II clinical trials. Other growth-factor-targeted drugs that have reached clinical development include STI571 and antibodies directed at the insulin-like growth factor pathway. Biologic therapies directed against these important receptors are promising. In this review we discuss challenges and opportunities for the development of growth-factor-targeted approaches for the treatment of breast cancer.
Nahta
Rita
R
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Hortobágyi
Gabriel N
GN
Esteva
Francisco J
FJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000502:physiology*; D017978:Receptors, Growth Factor; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D017978:Receptors, Growth Factor; D000068878:Trastuzumab