P-glycoprotein in breast cancer
Resistance to cytotoxic chemotherapy is a major impediment to the successful treatment of breast cancer. Adjuvant chemotherapy, though given under theoretically optimal conditions of low tumor bulk , often fails to eradicate micrometastasis. Once metastasis is grossly evident, most breast cancers have intrinsic resistance to single-agent chemotherapy. The response rate of such advanced disease to doxorubicin is less than 40%; the response rate to vinca alkyloids is only 21% [2,3]. Though higher initial response rates can be achieved with combination chemotherapy , essentially all breast cancers will become resistant to cytotoxic therapy. This might occur either through the outgrowth of resistant subclones under the selection pressure of chemotherapy , or through the induction of a resistant phenotype in surviving cancer cells. In either case, this resistance frequently includes a component of cross-resistance to unrelated agents, as second-line chemotherapy is marked by lower response rates and brief response durations .
KeywordsBreast Cancer Human Breast Cancer Cell Human Breast Cancer Cell Line Multiple Drug Resistance Breast Cancer Specimen
Unable to display preview. Download preview PDF.
- 1.Goldie, J.M. and Coldman, A.J. (1986). Chemotherapy and anatomy in breast cancer. Reviews on Endocrine-Related Cancer 23:17–22.Google Scholar
- 2.Tormey, D.C. (1975). Adriamycin (NSC 123127) in breast cancer. An overview of studies. Cancer Treat. Rep. 6:319–327.Google Scholar
- 6.Harris, J.R., Hellman, S., Cancellos, G.P. and Fisher, B. (1985). Cancer of the breast. In. Cancer. Principles and Practice of Oncology, eds. De Vita, V.T., Hellman, S., and Rosenberg, S.A., Lippincott, Philadelphia, p. 1159.Google Scholar
- 9.Willingham, M.C., Cornwell, M.M. Cardarelli, C.O., Gottesman, M.M. and Pastan I. (1986). Single cell analysis of daunomycin uptake and efflux in multidrug-resistant and -sensitive KB cells. Cancer Res. 45:5941–5946.Google Scholar
- 16.Schneider, S.L., Fuqua, S.A.W., Speeg, K.V. and McGuire, W.L. Isolation and characterization of an Adriamycin-resistant breast tumor cell line. Submitted.Google Scholar
- 20.Merkel, D.E., Fuqua, S.A.W., Tandon, A., Hill, S.M., Buzdar, A.U. and McGuire, W.L. Electrophoretic analysis of 248 clinical breast cancer specimens for P-glycoprotein over-expression or gene amplification. J. Clin. Oncol. In press.Google Scholar
- 25.Myers, C., Cowan, K., Sinha, B. and Chabner, B. (1987). The phenomenon of pleotropic drug resistance. In. Important Advances in Oncology, eds. De Vita, V.T., Hellman, S. and Rosenbery, S.A., Lippincott, Philadelphia, pp. 27–38.Google Scholar
- 30.Fuqua, S.A.W., Dimas, C., Von Hoff, D.D., Tandon, A.K., Kern, D.H. and McGuire, W.L. The techniques of Southern blot, RNA slot, and Western blot are not sensitive enough to detect P-glycoprotein amplification and/or expression in many human tumors. J. Clin. Oncol. In press.Google Scholar
- 31.Von Hoff, D.D., Clark, G.M., Stogdill, B.J., Sarosdy, M.F., O’Brien, M.T., Casper, J.T., Mattox, D.E., Page, C.P., Cruz, A.B. and Sandbeck, J.F. (1983). Prospective clinical trial of a human tumor cloning system. Cancer Res. 43:1926–1931.Google Scholar
- 43.Shenkenberg, T., Deacon, T., Dressler, L.G., Von Hoff, D.D. and McGuire, W.L. (1986). Increasing drug resistance in CHO cells by enriching for P-glycoprotein by flow cytometry. Proc. Am. Assoc. Cancer Res. 27:261 (Abstract).Google Scholar
- 45.Tandon, A., Clark, G., Ullrich, A., Slamon, D. and McGuire, W. (1988). Overexpression of the HER-l/neu oncogene predicts relapse and survival in Stage II human breast cancers. Proc. Amer. Soc. Clin. Oncol. (Abstract).Google Scholar