The current study examines the role of the epidermal growth factor gene (EGF) family in the pathogenesis of ovarian cancer. Gene amplification and protein overexpression of c-erbB2, a tyrosine kinase receptor, has been used as an indicator of poor prognosis in breast and ovarian cancer. We are studying the role of of c-erbB-2 as well as EGFR, erbB- 3 and erbB-4 in the proliferation of ovarian carcinoma cell lines and the maintenance of a transformed phenotype assaying for heterodimerization, heregulin stimulation of anchorage dependent and independent growth and examining constituitive and ligand induced phosphorylation. Elucidation of the role of these growth factor receptors may ultilmately lead to the development of gene therapies for the treatment of this disease. Our research examines the role of the EGF gene family of receptors and ligands in the growth of ovarian carcinoma cell lines. A fundamental understanding of growth factor/receptor interactions, cellular signaling and the biological effects on cell growth allows us to critically review INDs that use growth factors therapeutically. As documented by the literature, c-erbB-2 and EGFR have emerged as targets for tumor-directed therapy. Two INDs that use anti-cerbB-2 monoclonal antibodies for the treatment of breast and ovarian cancer are currently being reviewed. It is expected that additional therapies based on erbB-2 inhibition will be developed for clinical trials. Understanding the role of this family of receptors in malignant and non-malignant cell growth will help us evaluate the limitations and potential toxicities of the therapeutic agents directed against them.
