Accession Number : ADA311384

Title :   Reversal of Multidrug Resistance in Breast Cancer.

Descriptive Note : Annual rept. 15 Mar 95-14 Mar 96,

Corporate Author : FOX CHASE CANCER CENTER PHILADELPHIA PA

Personal Author(s) : Goldstein, Lori J.

PDF Url : ADA311384

Report Date : APR 1996

Pagination or Media Count : 14

Abstract : Our data shows that MDR1 gene expression is important in breast cancer resistance. The role of the MDR1 gene in breast cancer treatment will be further defined by sequentially determining MDR1 gene expression pre and post treatment with doxorubicin in the context of three prospective clinical trials. In addition, this study will allow a correlation of MDR1 gene expression and clinical outcome. To determine what level of MDR1 gene expression is clinically significant, various molecular methods of determining MDR1 gene expression, including immunohistochemistry and quantitative reverse transcription followed by polymerase chain reaction, will be evaluated. MDR can be reversed in vitro and we will test this hypothesis in a Phase 1 study of Cyclosporine A and quinine as MDR reversers of Vinblastine resistance. Together these studies will address the major goal of circumventing drug resistance in breast cancer. When the data of the MDR1 gene expression in breast cancer specimens from this proposal are available, clinical trials incorporating the modulators of MDR, Cyclosporine and quinine, will be designed for breast cancer as well. An alteration in drug efflux potentially may have an impact on response to chemotherapy and may result in improved survival for breast cancer patients. During the period between March 15, 1995 and March 14, 1996, we have outfitted our laboratory with staff, equipment, supplies and reagents, have been performing control experiments and have been pursuing activation of the various clinical trials to support this project. We now have some preliminary data on the expression of MDR1 and MRP (Multidrug resistant associated protein) in breast cancer specimens and normal adjacent breast tissue. Further follow-up of these patients is needed to determine the clinical significance of expression of these drug resistance genes.

Descriptors :   *CHEMOTHERAPY, *BREAST CANCER, EPITHELIUM, TISSUES(BIOLOGY), QUANTITATIVE ANALYSIS, POLYMERIZATION, GLYCOPROTEINS, IN VITRO ANALYSIS, CYTOPLASM, MOLECULAR BIOLOGY, GENES, CYTOTOXINS, PATIENTS, PHARMACOKINETICS, RESPONSE(BIOLOGY), MONOCLONAL ANTIBODIES, IN VIVO ANALYSIS, CHAIN REACTIONS, HISTOLOGY, RESISTANCE(BIOLOGY), ENDOTHELIUM, IMMUNOCHEMISTRY, MYOSIN, QUININE.

Subject Categories : Medicine and Medical Research
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE