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. 1993 Jan;67(1):24–29. doi: 10.1038/bjc.1993.5

Acquisition of platinum drug resistance and platinum cross resistance patterns in a panel of human ovarian carcinoma xenografts.

M Jones 1, J Siracky 1, L R Kelland 1, K R Harrap 1
PMCID: PMC1968234  PMID: 8427780

Abstract

In vivo models of acquired resistance to the platinum-based agents cisplatin (CDDP), carboplatin (CBDCA), iproplatin (CHIP) and tetraplatin have been established using a panel of six parent human ovarian carcinoma lines, two (HX/110 and PXN/87) being derived from previously untreated patients. Resistance has been generated to CDDP (three lines), CBDCA (one line), CHIP (three lines) and tetraplatin (one line) either by treatment in vivo or (for one line to CDDP) through exposure in vitro and subsequent transfer to mice. With the four tumours where resistance was generated using CDDP or CBDCA, a complete cross-resistance to the remaining platinum agents studied was observed. In contrast, in one of three lines with derived resistance to the platinum (IV) agent, CHIP, (PXN/951) a retention in sensitivity was observed with CDDP and CBDCA. Only one of the six parent tumour lines (PXN/100) was markedly sensitive to tetraplatin. Where resistance was generated to tetraplatin (PXN/100T) there was some retention of activity by CDDP. For the CDDP-resistant line established in vitro, there was a close agreement between the cross-resistance profile obtained in vitro vs that obtained in vivo. This tumour panel may be useful in the elucidation of cellular and molecular resistance mechanisms to platinum drugs operative in vivo. Moreover, as they appear to mimic the clinical observations of shared cross-resistance between CDDP, CBDCA and CHIP, they may represent valuable preclinical evaluation models for the discovery of drugs capable of conferring responses in CDDP-refractory ovarian cancer.

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Selected References

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  1. Andrews P. A., Howell S. B. Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance. Cancer Cells. 1990 Feb;2(2):35–43. [PubMed] [Google Scholar]
  2. Andrews P. A., Jones J. A., Varki N. M., Howell S. B. Rapid emergence of acquired cis-diamminedichloroplatinum(II) resistance in an in vivo model of human ovarian carcinoma. Cancer Commun. 1990;2(2):93–100. doi: 10.3727/095535490820874641. [DOI] [PubMed] [Google Scholar]
  3. Behrens B. C., Hamilton T. C., Masuda H., Grotzinger K. R., Whang-Peng J., Louie K. G., Knutsen T., McKoy W. M., Young R. C., Ozols R. F. Characterization of a cis-diamminedichloroplatinum(II)-resistant human ovarian cancer cell line and its use in evaluation of platinum analogues. Cancer Res. 1987 Jan 15;47(2):414–418. [PubMed] [Google Scholar]
  4. Ferrari A., Damia G., Erba E., Rossi C., Mandelli R., D'Incalci M. Characterization of a novel mouse reticular cell sarcoma M5076 subline resistant to cisplatin. Int J Cancer. 1989 Jun 15;43(6):1091–1097. doi: 10.1002/ijc.2910430623. [DOI] [PubMed] [Google Scholar]
  5. Goddard P. M., Valenti M. R., Harrap K. R. The role of murine tumour models and their acquired platinum-resistant counterparts in the evaluation of novel platinum antitumour agents: a cautionary note. Ann Oncol. 1991 Sep;2(8):535–540. doi: 10.1093/oxfordjournals.annonc.a058017. [DOI] [PubMed] [Google Scholar]
  6. Gore M. E., Fryatt I., Wiltshaw E., Dawson T., Robinson B. A., Calvert A. H. Cisplatin/carboplatin cross-resistance in ovarian cancer. Br J Cancer. 1989 Nov;60(5):767–769. doi: 10.1038/bjc.1989.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Harrap K. R., Jones M., Siracky J., Pollard L. A., Kelland L. R. The establishment, characterization and calibration of human ovarian carcinoma xenografts for the evaluation of novel platinum anticancer drugs. Ann Oncol. 1990;1(1):65–76. doi: 10.1093/oxfordjournals.annonc.a057678. [DOI] [PubMed] [Google Scholar]
  8. Hills C. A., Kelland L. R., Abel G., Siracky J., Wilson A. P., Harrap K. R. Biological properties of ten human ovarian carcinoma cell lines: calibration in vitro against four platinum complexes. Br J Cancer. 1989 Apr;59(4):527–534. doi: 10.1038/bjc.1989.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hospers G. A., Mulder N. H., de Jong B., de Ley L., Uges D. R., Fichtinger-Schepman A. M., Scheper R. J., de Vries E. G. Characterization of a human small cell lung carcinoma cell line with acquired resistance to cis-diamminedichloroplatinum(II) in vitro. Cancer Res. 1988 Dec 1;48(23):6803–6807. [PubMed] [Google Scholar]
  10. Kelland L. R., Jones M., Abel G., Valenti M., Gwynne J., Harrap K. R. Human ovarian-carcinoma cell lines and companion xenografts: a disease-oriented approach to new platinum anticancer drug discovery. Cancer Chemother Pharmacol. 1992;30(1):43–50. doi: 10.1007/BF00686484. [DOI] [PubMed] [Google Scholar]
  11. Kelland L. R., Mistry P., Abel G., Loh S. Y., O'Neill C. F., Murrer B. A., Harrap K. R. Mechanism-related circumvention of acquired cis-diamminedichloroplatinum(II) resistance using two pairs of human ovarian carcinoma cell lines by ammine/amine platinum(IV) dicarboxylates. Cancer Res. 1992 Jul 15;52(14):3857–3864. [PubMed] [Google Scholar]
  12. Kelland L. R., Murrer B. A., Abel G., Giandomenico C. M., Mistry P., Harrap K. R. Ammine/amine platinum(IV) dicarboxylates: a novel class of platinum complex exhibiting selective cytotoxicity to intrinsically cisplatin-resistant human ovarian carcinoma cell lines. Cancer Res. 1992 Feb 15;52(4):822–828. [PubMed] [Google Scholar]
  13. Mangioni C., Bolis G., Pecorelli S., Bragman K., Epis A., Favalli G., Gambino A., Landoni F., Presti M., Torri W. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464–1471. doi: 10.1093/jnci/81.19.1464. [DOI] [PubMed] [Google Scholar]
  14. McKeage M. J., Higgins J. D., 3rd, Kelland L. R. Platinum and other metal coordination compounds in cancer chemotherapy. A commentary on the sixth international symposium: San Diego, California, 23-26th January 1991. Br J Cancer. 1991 Oct;64(4):788–792. doi: 10.1038/bjc.1991.400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mistry P., Kelland L. R., Abel G., Sidhar S., Harrap K. R. The relationships between glutathione, glutathione-S-transferase and cytotoxicity of platinum drugs and melphalan in eight human ovarian carcinoma cell lines. Br J Cancer. 1991 Aug;64(2):215–220. doi: 10.1038/bjc.1991.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ozols R. F. Ovarian cancer: new clinical approaches. Cancer Treat Rev. 1991 Mar;18 (Suppl A):77–83. doi: 10.1016/0305-7372(91)90027-w. [DOI] [PubMed] [Google Scholar]
  17. Rose W. C., Basler G. A. In vivo model development of cisplatin-resistant and -sensitive A2780 human ovarian carcinomas. In Vivo. 1990 Nov-Dec;4(6):391–396. [PubMed] [Google Scholar]
  18. Schabel F. M., Jr, Skipper H. E., Trader M. W., Laster W. R., Jr, Griswold D. P., Jr, Corbett T. H. Establishment of cross-resistance profiles for new agents. Cancer Treat Rep. 1983 Oct;67(10):905–922. [PubMed] [Google Scholar]
  19. Seeber S., Osieka R., Schmidt C. G., Achterrath W., Crooke S. T. In vivo resistance towards anthracyclines, etoposide, and cis-diamminedichloroplatinum(II). Cancer Res. 1982 Nov;42(11):4719–4725. [PubMed] [Google Scholar]
  20. Sessa C., Vermorken J., Renard J., Kaye S., Smith D., ten Bokkel Huinink W., Cavalli F., Pinedo H. Phase II study of iproplatin in advanced ovarian carcinoma. J Clin Oncol. 1988 Jan;6(1):98–105. doi: 10.1200/JCO.1988.6.1.98. [DOI] [PubMed] [Google Scholar]
  21. Steel G. G., Courtenay V. D., Peckham M. J. The response to chemotherapy of a variety of human tumour xenografts. Br J Cancer. 1983 Jan;47(1):1–13. doi: 10.1038/bjc.1983.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Teicher B. A., Herman T. S., Holden S. A., Wang Y. Y., Pfeffer M. R., Crawford J. W., Frei E., 3rd Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. Science. 1990 Mar 23;247(4949 Pt 1):1457–1461. doi: 10.1126/science.247.4949.1457. [DOI] [PubMed] [Google Scholar]
  23. Waud W. R., Harrison S. D., Jr, Gilbert K. S., Laster W. R., Jr, Griswold D. P., Jr Antitumor drug cross-resistance in vivo in a cisplatin-resistant murine P388 leukemia. Cancer Chemother Pharmacol. 1991;27(6):456–463. doi: 10.1007/BF00685160. [DOI] [PubMed] [Google Scholar]
  24. Weiss G., Green S., Alberts D. S., Thigpen J. T., Hines H. E., Hanson K., Pierce H. I., Baker L. H., Goodwin J. W. Second-line treatment of advanced measurable ovarian cancer with iproplatin: a Southwest Oncology Group study. Eur J Cancer. 1991;27(2):135–138. doi: 10.1016/0277-5379(91)90470-x. [DOI] [PubMed] [Google Scholar]
  25. Zeller W. J., Frühauf S., Chen G., Keppler B. K., Frei E., Kaufmann M. Chemoresistance in rat ovarian tumours. Eur J Cancer. 1991;27(1):62–67. doi: 10.1016/0277-5379(91)90063-j. [DOI] [PubMed] [Google Scholar]

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