Growth Factor Receptor-Directed Therapy in Human Breast Cancer.
Annual rept. 1 Nov 94-31 Oct 95,
CALIFORNIA UNIV LOS ANGELES
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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.
- Medicine and Medical Research
- Anatomy and Physiology