Growth Factor Receptor-Directed Therapy in Human Breast Cancer
Abstract
Growth factors and their receptors are crucial in the regulation of breast cancer cell growth. Since the HER-2 growth factor receptor pathway is implicated in the progression of breast cancer in the clinic, we have targeted HER-2 receptors for therapeutic intervention. Our research goals are: 1) To induce human breast tumor remission with antibody to HER-2 receptor in combination with chemotherapeutic drugs. A therapeutic advantage of antibody to HER-2 receptor combined with drugs that damage breast cell DNA has been shown. In addition, the interaction between antireceptor antibodies and DNA-reactive chemotherapy drugs is schedule-dependent for optimal antitumor activity. 2) To assess the clinical significance of HER-2 gene expression in resistance to DNA-damaging drugs. By several different measures, modulation of DNA repair pathways occurs on activation of HER-2 receptor by anti-HER-2 antibody. Moreover, the adverse prognosis in patients with HER-2- overexpressing breast cancers may be related more to acquired rather than to intrinsic drug resistance. 3) To define the role of HER-2 and heregulin gene expression in antiestrogen resistance. Although HER-2-overexpressing breast cancers are resistant to estrogens and to tamoxifen, the latter cancers are sensitive to pure antiestrogens and to tamoxifen administered in combination with antibodies that down-regulate HER-2 receptors at the cell surface.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1997
- Accession Number
- ADB235501
Entities
People
- Richard J. Pietras
Organizations
- University of California, Los Angeles