Growth Factor Receptor-Directed Therapy in Human Breast Cancer.
Abstract
Growth factors and their receptors are crucial in regulation of breast cell growth. Since poor clinical outcome correlates with overexpression of HER-2 receptor in human breast cancer, we have initiated studies to target and exploit the HER-2 growth factor receptor pathway. The goals of this work are: 1) To induce 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 will be tested further with cisplatin and alkylating drugs to assess optimal treatment conditions. 2) To assess the clinical significance of HER-2 gene expression in resistance to DNA- damaging drugs. Modulation of DNA repair pathways is found to occur on activation of HER-2 receptor by anti-HER-2 antibody. Further investigation of this repair pathway and direct measure of drug sensitivity in breast cancer cells with and without HER-2 gene overexpression is underway. 3) To define the role of HER-2 and heregulin gene expression in antiestrogen resistance. Ligand for activation of HER-2 receptor, heregulin, and tumor cells bioengineered for production of heregulin will be used 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, 1995
- Accession Number
- ADA303513
Entities
People
- Richard J. Pietras
Organizations
- University of California, Los Angeles