Human Tumour Xenograft Models for Use with an In Vitro-Based, Disease-Oriented Antitumour Drug Screening Program

  • R. H. Shoemaker
  • T. L. McLemore
  • B. J. Abbott
  • D. L. Fine
  • E. Gorelik
  • J. G. Mayo
  • Ø. Fodstad
  • M. R. Boyd
Conference paper
Part of the ESO Monographs book series (ESO MONOGRAPHS)


Both short-term and long-term xenograft models may be useful in conjunction with an in vitro based disease-oriented drug screening program. Shortterm models may be most valuable in making initial assessments of the potential in vitro drug screening leads for in vivo use. We have previously shown that a substantial number of such leads may be subject to metabolic inactivation (1) and that this may be associated with a lack of therapeutic activity and a relative lack of toxicity in vivo. Certainly, rapid excretion or other pharmacologic factors may also render compounds inactive in vivo. Short-term as says may be very useful for identifying such compounds and thus setting priorities for further testing of in vitro drug leads in more rigorous longer-term models. Rational application of these longer-term models with particular attention to modeling of in situ vascular barriers, tumor microenvironment, and the natural history of the target diseases may facilitate identification and development of new drugs with significant clinical activity against the common adult solid tumors.


Nude Mouse Small Cell Lung Cancer Lung Cancer Cell Line Human Tumor Cell Line Athymic Nude Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Appel PL, Alley MC, Lieber MM, Shoemaker RH and Powis G: Metabolic stability of experimental chemotherapeutic agents in hepatocyte: tumor cell co-cultures. Can cer Chemother Pharmacol 1986 (17): 47–52CrossRefGoogle Scholar
  2. 2.
    Venditti JM: Preclinical drug development: Rationale and methods. Semin Oncol 1981 (8): 349–361PubMedGoogle Scholar
  3. 3.
    Staquet MJ, Byar DP, Green SB and Rozencweig M: Clinical predictivity of transplantable tumor systems in the selection of new drugs for solid tumors: Rationale for a three-stage strategy. Cancer Treat Rep 1983 (67): 753–765PubMedGoogle Scholar
  4. 4.
    Venditti JM, Wesley RA and Plowmann J: Current NCI preclinical screening in vivo results of tumor panel screening 1976–1982 and future directions. In: Garattini S, Goldin A and Hawkings S (eds) Advances in Pharmacology and Chemotherapy. Orlando, FL: Academic Press 1984: 1–20Google Scholar
  5. 5.
    Boyd MR, Shoemaker RH, Cragg GM and Suffness M: Future perspectives on the anticancer drug discovery program of the National Cancer Institute: Potential avenues for the investigation of marine biologicals. In: Jefford CW, Reinhart KL, Shield LS (eds) Pharmaceuticals and the Sea. Technomic Publ AG, Basel, in pressGoogle Scholar
  6. 6.
    Boyd MR, Shoemaker RH, Alley MC, Scudiero DA, Monks A, Fine DL, Mayo JG and Chabner BA: Drug development. In: Roth JA, Ruckdeschel JC and Weisenburger TH (eds) Thoracic Oncology. W. B. Saunders Co. In pressGoogle Scholar
  7. 7.
    Geran Rl, Greenberg NH, MacDonald MM, Schumacher AM and Abbott BJ: Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother Rep 1972 (3): 1–103Google Scholar
  8. 8.
    In vivo cancer models. 1984 NIH Publication No. 84–2635. US Department of Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, MDGoogle Scholar
  9. 9.
    Houghton JA, Cook RL, Lutz PJ and Houghton PJ: Childhood rhabdomyosarcoma xenografts: Responses to DNA-interacting agents and agents used in current clinical therapy. Eur J Cancer Clin Oncol 1984 (20): 955–960PubMedCrossRefGoogle Scholar
  10. 10.
    Steel GG, Courtenay VD and Peckham MJ: The response to chemotherapy of a variety of human tumor xenografts. BrJ Cancer 1983 (47): 1–13CrossRefGoogle Scholar
  11. 11.
    Fiebig HH, Schuchhardt C, Henss H, Fiedler L and Löhr GW: Comparison of tumor response in nude mice and in the patients. Behring Inst Mitt 1984 (74): 343–352PubMedGoogle Scholar
  12. 12.
    Fogh J, Fogh JM and Orfeo T: One hundred and twentyseven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst 1977 (59): 221–226PubMedGoogle Scholar
  13. 13.
    Sordat B, Fritsche R, Mach P, Carrel S, Ozello L and Cerotini JC: Morphological and functional evaluation of human solid tumors serially transplanted in nude mice. In: Rygaard J and Povlsen CO (eds) Proceedings of the first international workshop on nude mice. Stuttgart: Fischer 1974: 269–277Google Scholar
  14. 14.
    Sharkey FE and Fogh J: Metastasis of human tumors in athymic nude mice. Int J Cancer 1979 (24): 733–738PubMedCrossRefGoogle Scholar
  15. 15.
    Bellet RE, DannaV, Mastrangelo MJ and Berd D: Evaluation of a nude mouse-human tumor panel as a predictive secondary screen for cancer chemotherapeutic agents. J Natl Cancer Inst 1979 (63): 1185–1188PubMedGoogle Scholar
  16. 16.
    Bogden AE, Griffin W, Reich SD, Costanza ME and Cobb WR: Predictive testing with the subrenal capsule assay. Cancer Treat Rev 1984 (11): 113–124PubMedCrossRefGoogle Scholar
  17. 17.
    Giovanella BC, Stehlin JS Jr, Shepard RC and Williams LJ: Correlation between response to chemotherapy of human tumors in patients and in nude mice. Cancer 1983 (52): 1146–1152PubMedCrossRefGoogle Scholar
  18. 18.
    Epstein AL, Herman MM, Kim H, Dorfman FR and Kaplan HS: Biology of the human malignant lymphomas. Cancer 1976 (37): 2158–2176PubMedCrossRefGoogle Scholar
  19. 19.
    Bogden AE, Kelton DE, Cobb WR and Esber HJ: A rapid screening method for testing chemotherapeutic agents against human tumor xenografts. In: Houchens D and Ovejera T (eds) Proceedings of the symposium on the use of athymic (nude) mice in cancer research. New York: Gustav Fischer 1978Google Scholar
  20. 20.
    Bogden AE, Haskell PM, LePage DJ, Kelton DE, Cobb WR and Esber HJ: Growth of human tumor xenografts implanted under the renal capsule of normal immunocompetent mice. Exp Cell Biol 1979 (47): 281–293PubMedGoogle Scholar
  21. 21.
    Edelstein MB, Smink T, Ruiter DJ, Visser W and Van Putten LM: Improvements and limitations of the subrenal capsule assay for determining tumor sensitivity to cytostatic drugs. Eur J Cancer Clin Oncol 1984 (12): 1549–1556CrossRefGoogle Scholar
  22. 22.
    Edelstein MD, Fiebig HH, Smink T, Van Putten LM and Schuchhardt C: Comparison between macroscopic and microscopic evaluation of tumor responsiveness using the subrenal capsule assay. Eur J Cancer Clin Oncol 1983 19 (7): 995–1009CrossRefGoogle Scholar
  23. 23.
    Aamdal S, Fodstad Ø, Kaalhus O and Pihl A: Chemosensitivity profiles of human cancers assessed by the 6-day SRC assay on serially xenografted tumors. Int J Cancer 1986 (37): 579–587PubMedCrossRefGoogle Scholar
  24. 24.
    Bennett JA, Pilon VA and MacDowell RT: Evaluation of growth and histology of human tumor xenografts implant ed under the renal capsule of immunocompetent and immunodeficient mice. Cancer Res 1985 (45): 4963–4969PubMedGoogle Scholar
  25. 25.
    Fingert HJ, Mizrahi N, Bamberg MP and Cohen AM: Histologic studies of human tumors in the subrenal capsule assay (SRCA): Improved growth by enzymatic disaggregation. Proc Amer Assoc Cancer Res 1986 (27): 384Google Scholar
  26. 26.
    Gorelik E, Alley M and Shoemaker R: A new in vivo shortterm assay for evaluation of antitumor chemotherapeutic drugs. Proc Amer Assoc Cancer Res 1986 (27): 389Google Scholar
  27. 27.
    Gorelik E, Shoemaker R, Jarvis A, Ovejera A, Alley M, Duff R, Mayo J and Boyd M: A new short-term assay for in vivo evaluation of the effect of anticancer drugs on human tumor cells. (Manuscript in preparation)Google Scholar
  28. 28.
    Fidler IJ: General considerations for studies of experimental cancer metastasis. Meth Cancer Res 1978 (15): 399–439Google Scholar
  29. 29.
    Fidler IJ: Recent concepts of cancer metastasis and their implications for therapy. Cancer Treat Rep 1984 (68): 193–198PubMedGoogle Scholar
  30. 30.
    McLemore TL, Blacker PC, Gregg M, Jessee SE, Alley MC, Abbott BJ, Shoemaker RH, Litterst CC, Hubbard WC, Brennan RN, Fine DL, Eggleston JC, Mayo JG and Boyd MR: Intrabronchial implantation: A method for the orthotopic propagation of human lung tumors in athymic nude mice. Chest 1987 (91): 55–85CrossRefGoogle Scholar
  31. 31.
    McLemore TL, Blacker PC, Gregg M, Alley MC, Abbott BJ, Shoemaker RH, Liu MC, Litterst CC, Hubbard WC, Brennan RN, Fine DL, Bohlman ME, Eggleston JC, Mayo JG and Boyd MR: A novel intrapulmonary model for the orthotopic propagation of human lung cancers in athymic nude mice. Cancer Res 1987 (47): 5132–5140PubMedGoogle Scholar
  32. 32.
    Fine D, Shoemaker R, Gazdar A, Mayo J, Fodstad Ø, Boyd M, Abbott B and Donovan P: Metastasis models for human tumors in athymic mice: Useful models for drug development. Cancer Detect and Prev 1987 Suppl I: 291–299Google Scholar
  33. 33.
    Fidler IJ: Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Metastasis Rev 1986 (5): 24–29Google Scholar
  34. 34.
    Houchens DP, Ovejera AA, Riblet SM and Slagel DE: Human brain tumor xenografts in nude mice as a chemotherapy model. Eur J Cancer Clin Oncol 1983 (19): 799–805PubMedCrossRefGoogle Scholar
  35. 35.
    Silverberg E: Cancer Statistics. CA 1985 (35): 19–56PubMedCrossRefGoogle Scholar
  36. 36.
    Leob LA, Ernster VL and Warner KE: Smoking and lung cancer: An overview. Cancer Res 1984 (44): 5490–5958Google Scholar
  37. 37.
    Fodstad Ø, Aamdal S, Tveit KM and Pihl A: Lung colony formation in adult nude mice upon intravenous injection of cells from a human melanoma xenograft. Proc Amer Assoc Cancer Res 1982 (23): 881Google Scholar
  38. 38.
    Shoemaker R, Wolpert-DeFilippes M, Mayo J, Abbott B, Plowman J, Venditti J, Boyd M, Fodstad Ø, Ovejera A, Donovan P, Griswold D and Dykes D: Experimental chemotherapy studies of a human melanoma in nude mice using a survival endpoint. Proc Amer Assoc Cancer Res 1985 (26): 330Google Scholar
  39. 39.
    Hamilton TC, Young RC, Louie KG, Behrens BC, McKoy WM, Grotzinger KR, Ozols RF: Characterization of a xenograft model of human ovarian carcinoma which produces ascites and intraabdominal carcinomatosis in mice. Cancer Res 1984 (44): 5286–5290PubMedGoogle Scholar
  40. 40.
    Giovanella BC, Yim SO, Morgan AC, Stehlin JS and Williams LJ: Metastases of human melanomas transplanted in “nude” mice. J Natl Cancer Inst 1973 (50): 1051–1053PubMedGoogle Scholar
  41. 41.
    Kuroki M: A new human osteosarcoma strain (Os-Beppu) with a high rate of pulmonary metastasis in nude mice. Jpn J Clin Oncol 1984 (14): 49–56PubMedGoogle Scholar
  42. 42.
    Kerbel RS, Man MS, Dexter D: A model of human cancer metastasis: Extensive spontaneous and artificial metastasis of a human pigmented melanoma and derived variant sublines in nude mice. J Natl Cancer Inst 1984 (72): 93–108PubMedGoogle Scholar
  43. 43.
    Kozlowski JM, Fidler IJ, Campbell D, Xu XL, Kaighn ME and Hart IR: Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Res 1984 (44): 3522–3529PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • R. H. Shoemaker
    • 1
  • T. L. McLemore
    • 1
  • B. J. Abbott
    • 1
  • D. L. Fine
    • 2
  • E. Gorelik
    • 3
  • J. G. Mayo
    • 1
  • Ø. Fodstad
    • 4
  • M. R. Boyd
    • 1
  1. 1.Developmental Therapeutics Program, Division of Cancer TreatmentNational Cancer InstituteBethesdaUSA
  2. 2.Program Resources, Inc.National Cancer Institute - Frederick Cancer Research FacilityFrederickUSA
  3. 3.Pittsburgh Cancer InstitutePittsburghUSA
  4. 4.Institute for Cancer ResearchOslo 3Norway

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