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 achievements /aims include: (1) Induction of 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 is evident from initial studies. Antibodies to HER-2 receptor are undergoing testing with cisplatin and alkylating drugs to assess optimal treatment conditions for use in clinical trials. (2) Assessment of the clinical significance of HER-2 expression in resistance to DNA-damaging drugs. Reduced DNA repair is found on activation of HER-2 receptor by anti-HER-2 antibody. Investigation of DNA repair using a reporter gene and direct measure of drug sensitivity in breast cancer cells is ongoing. As compared to controls, HER-2-overexpressing tumors show more rapid regrowth after chemotherapy. (3) Defining tur role of HER-2 and heregulin gene expression in antiestrogen resistance. Ligand for activation of HER-2/HER-3 receptor dimers, heregulin, and tumor cells bicengineered for production of heregulin are in use to determine effects of autocrine activation of HER-2 receptor on sensitivity to antiestrogens. Studies with HER-2-overexpressing breast cancer cells are also in progress.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1996
- Accession Number
- ADA328031
Entities
People
- Richard J. Pietras
Organizations
- University of California, Los Angeles