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P-glycoprotein in breast cancer

  • Chapter
Book cover Drug Resistance in Cancer Therapy

Part of the book series: Cancer Treatment and Research ((CTAR,volume 48))

Abstract

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 [1], 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 [4], 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 [5], 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 [6].

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References

  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 

  3. Carter, S.K. (1976). Integration of chemotherapy into combined modality treatment of solid tumors. Cancer Treat. Rev. 3:141–179.

    Article  PubMed  CAS  Google Scholar 

  4. Cancellos, G.P., Pocock, S.J., Taylor, S.G. III, et al. 1976. Combination chemotherapy for metastatic breast carcinoma. Prospective comparison of multiple drug therapy with L-phenylalanine mustard. Cancer 38:1882–1886.

    Article  Google Scholar 

  5. Goldie, J.H. and Coldman, A.J. (1979). A mathematical model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat. Rep. 63:1727–1733.

    PubMed  CAS  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 

  7. Ling, V. (1975). Drug resistance and membrane alterations in mutants of mammalian cells. Can. J. Genet. Cytol. 17:503–515.

    PubMed  CAS  Google Scholar 

  8. Juliano, R.L. and Ling, V. (1976). A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta 455:152–162.

    Article  PubMed  CAS  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 

  10. Safa, A.R., Glover, C.J. and Meyers, M.B. (1986). Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J. Biol. Chem. 261:6137–6140.

    PubMed  CAS  Google Scholar 

  11. Roninson, LB., Abelson, H.T., Housman, D.E., Howell, N. and Varshavsky, A. (1984). Amplification of specific DNA sequences correlates with multidrug resistance in Chinese hamster cells. Nature 309:626–628.

    Article  PubMed  CAS  Google Scholar 

  12. Shen D.W., Fojo, A., Chin, J.E., Roninson, LB., Richart, N., Pastan, I. and Gottesman, M.M. (1986). Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification. Science 232:643–645.

    Article  PubMed  CAS  Google Scholar 

  13. Hamada, H., and Tsuruo, T. (1986). Functional role for the 170- to 180-kDa glycoprotein specific to drug resistant tumor cells as revealed by monoclonal antibodies. Proc. Natl. Acad. Sci. USA 83:7785–7789.

    Article  PubMed  CAS  Google Scholar 

  14. Tsuruo, T., Iida, H., Tsukagoshi, S. and Sakurai, Y. (1982). Increased accumulation of vincristine and Adriamycin in drug resistant P388 tumor cells following incubation with calcium antagonists and calmodulin inhibitors. Cancer Res. 42:4730–4733.

    PubMed  CAS  Google Scholar 

  15. Rogan, A.M., Hamilton, T.C. and Young, R.C. (1984). Reversal of adriamycin resistance by verapamil in human ovarian cancer. Science 224:994–996.

    Article  PubMed  CAS  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 

  17. Van der Bliek, A.M., Van der Velde-Koerts, T., Ling, V. and Vorst, P. (1986). Over-expression and amplification of five genes in a multidrug-resistant Chinese hamster ovary cell line. Mol. Cell. Biol. 6:1671–1678.

    PubMed  Google Scholar 

  18. Lathan, B., Edwards, D.P., Dressler, L.G., Von Hoff, D.D. and McGuire, W.L. (1985). Immunologic detection of Chinese hamster ovary cells expressing a multidrug resistance phenotype. Cancer Res. 45:5064–5069.

    PubMed  CAS  Google Scholar 

  19. Fuqua, S.A.W., Moretti-Rojas, I.M., Schneider, S.L. and McGuire, W.L. (1987). P-glycoprotein expression in human breast cancer cells. Cancer Res. 47:2103–2106.

    PubMed  CAS  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 

  21. Batist, G., Tulpule, A., Sinha, B.K., Katki, A.G., Myers, C.E. and Cowan, K.E. (1986). Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells. J. Biol. Chem. 261:15544–15549.

    PubMed  CAS  Google Scholar 

  22. Fairchild, C.R., Ivy, S.P., Kao-Shan, C.-S., Whang-Peng, J., Rosen, N., Israel, M.A., Melera, P.W., Cowan, K.H. and Goldsmith, M.E. (1987). Isolation of amplified and overexpressed DNA sequences from Adriamycin-resistant human breast cancer cells. Cancer Res. 47:5141–5148.

    PubMed  CAS  Google Scholar 

  23. Roninson, LB. (1983). Detection and mapping of homologous, repeated and amplified DNA sequences by DNA renaturation in agarose gels. Nucleic Acids Res. 11:5413–5431.

    Article  PubMed  CAS  Google Scholar 

  24. Cowan, K.H., Batist, G., Tulpule, A., Sinha, B.K. and Myers, C.E. (1986). Similar biochemical changes associated with multidrug resistance in human breast cancer cells and carcinogen-induced resistance to xenobiotics in rats. Proc. Natl. Acad. Sci. USA 83:9328–9332.

    Article  PubMed  CAS  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 

  26. Thorgeirsson, S.S. Huber, B.E., Sorrell, S., Fojo, A., Pastan, I. and Gottesman, M.M. (1987). Expression of the multidrug-resistant gene in hepatocarcinogenesis and regenerating rat liver. Science 236:1120–1122.

    Article  PubMed  CAS  Google Scholar 

  27. Yeh, G.C., Occhipinti, S.J., Cowan, K.H., Chabner, B.A. and Myers, C.E. (1987). Adriamycin resistance in human tumor cells associated with marked alterations in the regulation of the hexose monophosphate shunt and its response to oxidant stress. Cancer Res. 47:5994–5999.

    PubMed  CAS  Google Scholar 

  28. Sinha, B.K., Katki, A.G., Batist, G., Cowan, K.H. and Myers, C.E. (1987). Differential formation of hydroxyl radicals by Adriamycin in sensitive and resistant MCF-7 human breast cancer cells; implications for the mechanism of action. Biochemistry 26:3776–3781.

    Article  PubMed  CAS  Google Scholar 

  29. Hortobagyi, G.N., Blumenschein, G.T., Spanos, W., Montague, E.D., Buzdar, A.V., Yap, H.-Y. and Schell, F. (1983). Multimodal treatment of locoregionally advanced breast cancer. Cancer 51:763–768.

    Article  PubMed  CAS  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 

  32. Kern, D.H., Drogemuller, C.R., Kennedy, M.C, Hildebrand-Zanki, S.U., Tanigwa, N. and Sondak, V.K. (1985). Development of a miniaturized, improved nucleic acid precursor incorporation assay for chemosensitivity testing of human solid tumors. Cancer Res. 45:5436–5441.

    PubMed  CAS  Google Scholar 

  33. Gerlach, J.H., Bell, D.R., Karakousis, C., Slocum, H.K., Kartner, N., Rustum, Y.M., Long, V. and Baker, R.M. (1987). P-glycoprotein in human sarcoma; evidence for multidrug resistance. J. Clin. Oncol. 5:1452–1460.

    PubMed  CAS  Google Scholar 

  34. Pastan, I. and Gottesman, M. (1987). Multiple drug resistance in human cancer. New Engl. J. Med. 316:1388–1393.

    Article  PubMed  CAS  Google Scholar 

  35. Fojo, A.T., Ueda, K., Slamon, D.J., Poplack, D.G., Gottesman, M.M. and Pastan, I. (1987). Expression of a multidrug-resistance gene in human tumors and tissues. Proc. Natl. Acad. Sci. USA 84:265–269.

    Article  PubMed  CAS  Google Scholar 

  36. Farber, E. (1984). Cellular biochemistry of the stepwise development of cancer with chemicals; GHA Clowes Memorial Lecture. Cancer Res. 44:5463–5474.

    PubMed  CAS  Google Scholar 

  37. Fojo, A.T., Shen, D.-W., Mickley, L.A., Pastan, I. and Gottesman, M.M. (1987). Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug-resistance gene. J. Clin. Oncol. 5:1922–1927.

    PubMed  CAS  Google Scholar 

  38. Brambilla, C., De Lena, M., Rossi, A., Valagussa, P. and Bonadonna, G. (1976). Response and survival in advanced breast cancer after two non-cross-resistant combinations. Br. Med. J. 1:801–804.

    Article  PubMed  CAS  Google Scholar 

  39. Tormey, D.C., Gelman, R., Band, P.R., Sears, M., Rosenthal, S.N., De Wys, W., Perlia, C. and Rice, M.A. (1982). Comparison of induction chemotherapies for metastatic breast cancer. Cancer 50:1235–1244.

    Article  PubMed  CAS  Google Scholar 

  40. Yau, J.C., Yap, Y.-Y., Buzdar, A.U., Hortobagyi, G.N., Bodey, G.P. and Blumenschein, G.R. (1985). A comparative randomized trial of vinca alkyloids in patients with metastatic breast carcinoma. Cancer 55:337–340.

    Article  PubMed  CAS  Google Scholar 

  41. Garewal, H.S., Brooks, R.J., Jones, S.E. and Miller, T.P. (1983). Treatment of advanced breast cancer with mitomycin C combined with vinblastine or vindesine. J. Clin. Oncol. 1:772–775.

    PubMed  CAS  Google Scholar 

  42. Yap, H.-Y., Blumenschein, G.R., Keating, M.J., Hortobagyi, G.N., Tashima, C.K. and Loo, T.L. (1980). Vinblastine given as a continuous 5-day infusion in the treatment of refractory advanced breast cancer. Cancer Treat. Rep. 64:279–283.

    PubMed  CAS  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 

  44. Slamon, D.J., Clark, G.M., Wong, S.G., Levin, W.J., Ullrich, A. and McGuire, W.L. (1987). Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182.

    Article  PubMed  CAS  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 

  46. Osborne, C.K., Yochmowitz, M.G., Knight, W.A., III, and McGuire, W.L. (1980). The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 46:2884–2888.

    Article  PubMed  CAS  Google Scholar 

  47. Bell, D.R., Gerlach, J.H., Kartner, N., Buick, R.N. and Ling, V. (1985). Detection of P-glycoprotein in ovarian cancer: A molecular marker associated with multidrug resistance. J. Clin. Oncol. 3:311–315.

    PubMed  CAS  Google Scholar 

  48. Gerlach, J.M., Bell, D.R., Karabousis, C., Slocum, H.K., Kartner, N., Rustum, Y.M., Ling, V. and Baker, R.M. (1987). P-glycoprotein in human sarcomas: Evidence for multidrug resistance. J. Clin. Oncol. 5:1452–1460.

    PubMed  CAS  Google Scholar 

  49. Ozols, R.F., Cunnion, R.E., Klecker, W.R., Jr., Hamilton, J.C., Ostchega, Y., Parrilo, J.E. and Young, R.C. (1987). Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J. Clin. Oncol. 5:641–647.

    PubMed  CAS  Google Scholar 

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Authors
  1. Douglas E. Merkel
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  2. Suzanne A. W. Fuqua
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  3. William L. McGuire
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Editor information

Editors and Affiliations

  1. Fox Chase Cancer Center, 7701 Burholme Auenue, Philadelphia, PA, 19111, USA

    Robert F. Ozols M.D., Ph.D.

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© 1989 Kluwer Academic Publishers

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Merkel, D.E., Fuqua, S.A.W., McGuire, W.L. (1989). P-glycoprotein in breast cancer. In: Ozols, R.F. (eds) Drug Resistance in Cancer Therapy. Cancer Treatment and Research, vol 48. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1601-5_7

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  • DOI: https://doi.org/10.1007/978-1-4613-1601-5_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8886-2

  • Online ISBN: 978-1-4613-1601-5

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