Accession Number : ADA303513

Title :   Growth Factor Receptor-Directed Therapy in Human Breast Cancer.

Descriptive Note : Annual rept. 1 Nov 94-31 Oct 95,

Corporate Author : CALIFORNIA UNIV LOS ANGELES

Personal Author(s) : Pietras, Richard J.

PDF Url : ADA303513

Report Date : NOV 1995

Pagination or Media Count : 35

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.

Descriptors :   *DEOXYRIBONUCLEIC ACIDS, *CHEMOTHERAPY, *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *BREAST CANCER, MEASUREMENT, ACTIVATION, OPTIMIZATION, PRODUCTION, DAMAGE, HUMANS, RESISTANCE, NEOPLASMS, TARGETS, SENSITIVITY, REPAIR, ALKYLATION, GENES, DRUGS, MODULATION, CELLS(BIOLOGY).

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE