Accession Number : ADA328031

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

Descriptive Note : Annual rept. 1 Nov 95-31 Oct-96,

Corporate Author : CALIFORNIA UNIV LOS ANGELES

Personal Author(s) : Pietras, Richard J.

PDF Url : ADA328031

Report Date : NOV 1996

Pagination or Media Count : 36

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.

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

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE