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Patient-Derived Xenograft Models for Human Cancer: The Freiburg Experience

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Patient-Derived Mouse Models of Cancer

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

This chapter reviews the almost 40-year Freiburg experience with patient-derived mouse models of cancer. More than 3,000 patient tumors of all major types have been implanted in nude nice. Take rates varied with tumor types, with GI tumors high and hormone-dependent tumors low. Tumors became established after 2-3 passages with high-grade tumors having the highest establishment rate. We correlated drug response in the patient-derived mouse models with the donor patient and found a very high level of concordance for both drug resistance and sensitivity. However, the time necessary to establish the patient-derived models makes them more suitable to determine 2nd line therapy rather than first line. Among the tumors established, 240 were found to have very reproducible behavior, could be cryo-preserved and recovered from liquid nitrogen storage at very high frequency and were extensively characterized with regard to drug sensitivity and by genomic profiling. This set of 240 patient-derived tumors has proven to be highly-useful for cancer drug discovery and evaluation for laboratories around the world and has proven to be a resource without equal.

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References

  1. Isaacson HJ, Cattanach BM. Report. Mouse News Letter. 1962;27:31.

    Google Scholar 

  2. Flanagan SP. “Nude”, a new hairless gene with pleiotropic effects in the mouse. Genet Res. 1966;8:295–309.

    Article  CAS  PubMed  Google Scholar 

  3. Green MC. Genetic variants and strains of the laboratory mouse. In: Bastert G, Fortmeyer HP, Schmitt-Matthiesen H, editors. Thymus aplastic nude mice and rats in clinical oncology. Stuttgart: Fischer; 1981. p. 174–5, 280–1.

    Google Scholar 

  4. Pantelouris EM. Absence of the thymus in a mouse mutant. Nature. 1968;217:370.

    Article  CAS  PubMed  Google Scholar 

  5. Rygaard J, Povlsen CO. Heterotransplantation of a human malignant tumor to the mouse mutant nude. Acta Pathol Microbiol Scand. 1969;77:758–66.

    Article  CAS  PubMed  Google Scholar 

  6. Sordat B, Tamaoki N, Povlsen CO. List of human tumors transplanted to nude mice. In: Nomura T, et al., editors. Second international workshop on nude mice. New York, Stuttgart: Fischer; 1977. p. 587–95.

    Google Scholar 

  7. Sordat B, Merenda C, Carrel S. Invasive growth and dissemination of human solid tumors and malignant cell lines grafted subcutaneously to new-born nude mice. In: Nomura T, et al., editors. Proceedings of the second international workshop on nude mice. New York, Stuttgart: Fischer; 1977. p. 313–26.

    Google Scholar 

  8. Giovanella BC, et al. Development of invasive tumors in the nude mouse after injection of cultured human melanoma cells. J Natl Cancer Inst. 1972;48:1531–3.

    Google Scholar 

  9. Giovanella BC, Stehlin JS. Assessment of the malignant potential of cultured cells by injection in nude mice. In: Rygaard J, Povlsen CO, editors. Proceedings of the first international workshop on nude mice. Stuttgart: Fischer; 1974. p. 279–84.

    Google Scholar 

  10. Povlsen CO, Rygaard J. Effects of cyclophosphamide (EndoxanR) on a Burkitt’s lymphoma serially grown in nude mice. In: Rygaard J, Povlsen CO, editors. Proceedings of the first international workshop on nude mice. Stuttgart: Fischer; 1974. p. 285–92.

    Google Scholar 

  11. Povlsen CO, Jacobsen GK. Chemotherapy of a human malignant melanoma transplanted in nude mouse. Cancer Res. 1975;35:2790–6.

    CAS  PubMed  Google Scholar 

  12. Rygaard J. Immunbiology of the mouse mutant “nude”. Preliminary investigations. Acta Pathol Microbiol Scand. 1969;77:761–2.

    Article  CAS  PubMed  Google Scholar 

  13. Shaffer CF, Reed ND, Jutila JW. Comparative survival of skin grafts from several donor species on congenitally athymic mice. Transplant Proc. 1973;5:711–2.

    CAS  PubMed  Google Scholar 

  14. Manning DD, Reed ND, Shaffer CF. Maintenance of skin xenografts of widely divergent phylogenetic origin on congenitally athymic (nude) mice. J Exp Med. 1973;138:488–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rygaard J. Skin grafts in nude mice. Third fate of grafts from man and donors of other taxonomic classes. Acta Pathol Microbiol Scand. 1974;82:105–12.

    CAS  Google Scholar 

  16. Reed ND, Manning DD. Long term maintenance of normal human skin on congenitally athymic (nude) mice. Proc Soc Exp Biol Med. 1973;143:350.

    Article  CAS  PubMed  Google Scholar 

  17. Rygaard J, Friis CW. The husbandry of mice with congenitally absence of the thymus (nude mice). Z Versuchstierkd. 1974;16:1–10.

    CAS  PubMed  Google Scholar 

  18. Rygaard J, Povlsen CO. Proceedings of the first international workshop on nude mice. Stuttgart: Fischer; 1974.

    Google Scholar 

  19. Nomura T, et al. Proceedings of the second international workshop on nude mice. Stuttgart: Fischer; 1978.

    Google Scholar 

  20. Sparrow S. Immunodeficient animals in cancer research. London: Macmillan; 1980.

    Book  Google Scholar 

  21. Bastert G, Fortmeyer HP, Schmidt-Matthiesen H. Thymus aplastic nude mice and rats in clinical oncology. Stuttgart: Fischer; 1981.

    Google Scholar 

  22. Reed ND. Proceedings of the third international workshop on nude mice. Stuttgart: Fischer; 1982.

    Google Scholar 

  23. Prabhakaran K, Harris EB, Kirchheimer WF. Hairless mice, human leprosy and thymus-derived lymphocytes. Experientia. 1975;31:784.

    Article  CAS  PubMed  Google Scholar 

  24. Kohsaka K, et al. Nude mice as a model for chemotherapy of leprosy. In: Reed ND, editor. Proceedings of the third international workshop on nude mice. Stuttgart: Fischer; 1982. p. 59–66.

    Google Scholar 

  25. Armstrong D, Walzer P. Experimental infections in the nude mouse. In: Fogh J, Giovanella BC, editors. The nude mouse in experimental and clinical research. New York, San Francisco, London: Academic Press; 1978. p. 477–89.

    Google Scholar 

  26. Waki S, Suzuki M. A study of malaria immunobiology using nude mice. In: Nomura T, et al., editors. Proceedings of the second international workshop on nude mice. The potentialities and limitations of the nude mouse. New York, Stuttgart: Fischer; 1977. p. 37–44.

    Google Scholar 

  27. Waki S, Suzuki M. T-independent antibody production in nude mice infected with a rodent malaria parasite (Plasmodium berghei). In: Reed ND, editor. Proceedings of the first international workshop on nude mice. New York, Stuttgart: Fischer; 1982. p. 91–102.

    Google Scholar 

  28. Brooks BO, Reed ND. Trypanosoma musculi infections of nude mice. In: Reed ND, editor. Proceedings of the first international workshop on nude mice. New York, Stuttgart: Fischer; 1982. p. 111–22.

    Google Scholar 

  29. Jacobsen GK, Reed ND. The immune response of congenitally athymic (nude) mice to the intestinal nematode Nippostrongylus brasiliensis. Proc Soc Exp Biol Med. 1974;147:667.

    Article  Google Scholar 

  30. Mitchell GF, Holmes MC. Nude mice in the study of susceptibility and response to infection with metazoan and protozoan parasites. In: Reed ND, editor. Proceedings of the first international workshop on nude mice. New York, Stuttgart: Fischer; 1981. p. 1–10.

    Google Scholar 

  31. Kamiya M, et al. Characteristic responses of nude mice in angiostrongyliasis and echinococcosis. In: Reed ND, editor. Proceedings of the first international workshop on nude mice. New York, Stuttgart: Fischer; 1982. p. 493–504.

    Google Scholar 

  32. Fortmeyer HP. Thymusaplastische Maus (nu/nu) - thymusaplastische Ratte (rnu/rnu) - Haltung, Zucht, Versuchsmodelle, vol. 8. Berlin: P. Parey; 1981.

    Google Scholar 

  33. Wortis HH, Nehlsen S, Owen JJ. Abnormal development of the thymus in “nude” mice. J Exp Med. 1971;134:681–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cordier AC. Ciliogenesis and ciliary anomalies in the thymic cysts of “nude” mice. Cell Tissue Res. 1974; 148:397–406.

    Google Scholar 

  35. Groscurth P, Müntener M, Töndury G. The postnatal development of the thymus in the nude mouse. Light microscopic observations. In: Rygaard J, Povlsen CO, editors. Proceedings of the first international workshop on nude mice. New York, Stuttgart: Fischer; 1974. p. 31–6.

    Google Scholar 

  36. Hair J. The morphogenesis of thymus in nude and normal mice. Proceedings of the first international workshop on nude mice. Stuttgart: Fischer; 1974. p. 23–30.

    Google Scholar 

  37. Rychter Z, Holub M, Vanecek R. Topical and quantitative analysis of the thymus region in the nude mouse. Folia Biol (Praha). 1978;24:414–5.

    CAS  Google Scholar 

  38. Holub M, Rosmann P, Mandi B. The dysgenetic thymic complex of the nude mouse. Fol Biol (Praha). 1978;24:416–8.

    CAS  Google Scholar 

  39. Scheiff JM, Cordier A. Etude quantitative du thymus de la souris heterozygote pour le gene nu. Bull Assoc Anat. 1974;58:163.

    Google Scholar 

  40. Zipore BD, Trainin N. Defective capacity of bone marrow from nude mice to restore lethally irradiated recipients. Blood. 1973;42:671–8.

    Google Scholar 

  41. Holub M, et al. Lymphatic tissues and antibody-forming cells of athymic (nude) mice. Z Immunitatsforsch Exp Klin Immunol. 1974;146:322–33.

    CAS  PubMed  Google Scholar 

  42. Dolenska S, Holub M, Mandi B. Bone marrow stem cell potential in mice earing the nu gene. Folia Biol (Praha). 1978;24:421–3.

    CAS  Google Scholar 

  43. Raff MC, Wortis HH. Thymus dependence of o-bearing cells in the peripheral lymphoid tissues of mice. Immunology. 1970;18:931–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Yunker VM, Gruntenko EV, Moroskova TS. Leucocyte blood composition in mice C3H/He Nu/Nu, C3H/He. Fol Biol (Praha). 1978;24:437.

    CAS  Google Scholar 

  45. Weihe WH. Effects of air velocity on hairless mice. J Physiol Paris. 1971;63:452.

    CAS  PubMed  Google Scholar 

  46. Pantelouris EM, Lintern-Moore S. Physiological studies on the nude mouse. In: Fogh J, Giovanella BC, editors. The nude mouse in experimental and clinical research. New York, San Francisco, London: Academic Press; 1978. p. 51–73.

    Google Scholar 

  47. Fortmeyer HP, Bastert G. Breeding and maintenance of nu/nu mice and rnu/rnu rats. In: Bastert G, Fortmeyer HP, Schmidt-Matthiesen H, editors. Thymusaplastic nude mice and rats in clinical oncology. Stuttgart: Fischer; 1981. p. 25–38.

    Google Scholar 

  48. Loor F, Roelants GE. High frequency of T lineage lymphocytes in nude mouse spleen. Nature. 1974;251:229.

    Article  CAS  PubMed  Google Scholar 

  49. Loor F, Roelants GE. Immunofluorescence studies of a possible prethymic T-cell differentiation in congenitally athymic (nude) mice. Ann N Y Acad Sci. 1975;254:226–41.

    Article  CAS  PubMed  Google Scholar 

  50. Sato VL, Waksal SD, Herzenberg LA. Identification and separation of pre-T-cells from nu/nu mice. Differentiation by preculture with thymic reticuloepithelial cells. Cell Immunol. 1976;24:173–85.

    Article  CAS  PubMed  Google Scholar 

  51. Sprent J. Migration and lifespan of circulating B-lymphocytes. In: Rygaard J, Povlsen CO, editors. Proceedings of the first international workshop on nude mice. New York, Stuttgart: Fischer; 1974. p. 11–12.

    Google Scholar 

  52. Meerpohl HG, et al. Cytotoxic capacities of macrophages in nu/nu mice. In: Bastert G, Fortmeyer HP, Schmidt-Matthiesen H, editors. Stuttgart: Fischer; 1981. p. 57–62.

    Google Scholar 

  53. Luzzati AL, Jacobson EB. Serum immunoglobulin levels in nude mice. Eur J Immunol. 1972;2:473–4.

    Article  CAS  PubMed  Google Scholar 

  54. Salomon JC, Bazin H. Low levels of some serum immunoglobulin classes in nude mice. Rev Eur Etud Clin Biol. 1972;17:880–2.

    CAS  PubMed  Google Scholar 

  55. Kindred B. Antibody response in genetically thymusless nude mice injected with normal thymus cells. J Immunol. 1971;107:1291–5.

    CAS  PubMed  Google Scholar 

  56. Bloemmen J, Eyssen H. Immunglobulin levels of sera of genetically thymusless (nude) mice. Eur J Immunol. 1973;3:117–8.

    Article  CAS  PubMed  Google Scholar 

  57. Jacobsen GK, Povlsen CO, Rygaard J. Effects of thymus grafts in nude mice transplanted with human malignant tumors. In: Reed ND, editor. Proceedings of the third international workshop on nude mice. New York, Stuttgart: Fischer; 1982. p. 493–504.

    Google Scholar 

  58. Fiebig HH. Wachstum und Chemotherapie menschlicher Tumoren - vorwiegend Dickdarm-, Magen- und Bronchialkarzinome - in der thymusaplastischen Nacktmaus. Habilitationsschrift, Universität Freiburg; 1983.

    Google Scholar 

  59. Berger DP. Proliferation and vascularization humaner solider Tumoren als Grundlage neuer Therapieansätze. Habilitationsschrift, Universität Freiburg; 1995.

    Google Scholar 

  60. Burger AM, et al. The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function. Cancer Res. 2005;65(4):1489–96.

    Article  CAS  PubMed  Google Scholar 

  61. Wirth GJ, et al. Microarrays of 41 human tumor cell lines for the characterization of new molecular targets: expression patterns of Cathepsin B and the transferrin receptor. Oncology. 2006;71:86–94.

    Article  CAS  PubMed  Google Scholar 

  62. Fiebig HH, Löhr GW. Transplantation of human sarcomas in nude mice and development of tumor models for chemotherapy. Curr Chemother Immunother. 1982. p. 1280–2.

    Google Scholar 

  63. Fiebig HH, Löhr GW. Wachstum menschlicher Malignome und Entwicklung von Tumormodellen in der thymusaplastischen Nacktmaus. Med Welt. 1984;35:52–8, 81–6.

    Google Scholar 

  64. Fiebig HH, et al. Biological characterization and chemotherapy of human colorectal, stomach and esophageal cancers growing in nude mice. In: Klein HO, editor. Advances in the chemotherapy of gastrointestinal cancer. Erlangen: Perimed Fachbuch; 1984. p. 53–73.

    Google Scholar 

  65. Fiebig HH, et al. Development and characterization of 51 human tumor models for large bowel, stomach and esophageal cancers. Dig Surg. 1984;1:225–35.

    Article  Google Scholar 

  66. Fiebig HH, Neumann H, et al. Development of 3 human small cell lung cancer models in nude mice. Recent Results Cancer Res. 1985;97:77–86.

    Article  CAS  PubMed  Google Scholar 

  67. Berger DP, Fiebig HH, Winterhalter BR. Establishment and characterization of human tumor xenograft models in nude mice. In: Fiebig HH, Berger DP, editors. Immunodeficient mice in oncology. Basel: Karger; 1992. p. 23–46.

    Google Scholar 

  68. Fiebig HH, et al. Combined in vitro/in vivo test procedure with human tumor xenografts. In: Fiebig HH, Berger DP, editors. Immunodeficient mice in oncology. Basel: Karger; 1992. p. 321–51.

    Google Scholar 

  69. Fiebig HH, Dengler WA, Roth T. Human tumor xenografts: Predictivity, characterization and discovery of new anticancer agents. In: Fiebig HH, Burger AM, editors. Relevance of tumor models for anticancer drug development. Contrib Oncol Basel: Karger. 1999;54:29–50.

    Google Scholar 

  70. Fiebig HH, et al. Biological characterization and chemotherapy of human colorectal comparison of tumor response in nude mice and in the patients. Behring Inst Mitt. 1984;74:343–52.

    Google Scholar 

  71. Fiebig HH. Comparison of tumor response in nude mice and in the patients. In: Winograd B, Peckham MJ, Pinedo HM, editors. Human tumor xenografts in anticancer drug development. Berlin: Springer; 1988. p. 25–30.

    Google Scholar 

  72. Fiebig HH, et al. Comparison of tumor response in nude mice and in the patients. Behring Inst Mitt. 1984;74:343–52.

    Google Scholar 

  73. Fiebig HH, Winterhalter BR, Scholz CC. Limited potential of the human tumor-nude mouse system for pretherapeutic drug testing. Zeitschr Antimikrob Antineoplast Chemoth. 1988;6(1):17–22.

    CAS  Google Scholar 

  74. Scholz CC, Fiebig HH, Winterhalter BR, Berger DP, Henss H. Correlation of drug response in patients and in the clonogenic assay using solid human tumor xenografts. Eur J Cancer Clin Oncol. 1990;26:901–5.

    Article  CAS  Google Scholar 

  75. Henss H, et al. Clonal growth of human tumor xenografts, first experiences in drug testing. J Cancer Res Clin Oncol. 1984;108:233–5.

    Google Scholar 

  76. Fiebig HH, et al. Colony assay with human tumor xenografts, murine tumors and human bon marrow. Potential for anticancer drug development. Eur J Cancer Clin Oncol. 1987;23:937–48.

    Article  CAS  PubMed  Google Scholar 

  77. Fiebig HH, Maier A, Burger AM. Clonogenic assay with established human tumor xenografts: correlation of in vitro to in vivo activity as a basis for anticancer drug discovery. Eur J Cancer. 2004;40:802–20.

    Article  CAS  PubMed  Google Scholar 

  78. Berger DP, et al. The clonogenic assay with human tumor xenografts. Evaluation, predictive value and application for drug screening. Ann Oncol. 1990;1:333–41.

    Article  CAS  PubMed  Google Scholar 

  79. Hinkelbein W, et al. Intrinsic thermosensitivity of various human tumors. In: Hinkelbein W, et al., editors. Preclinical hyperthermia. Berlin: Springer; 1988;109:198–202.

    Google Scholar 

  80. Hinkelbein W, et al. Fractionated irradiation under ambient conditions of human NSCLC transplanted into nude mice. Effect of different fractionation schedules and of radiotherapy and vindesine. Strahlenther Onkol. 1989;165:519–20.

    CAS  PubMed  Google Scholar 

  81. Neumann HA, Fiebig HH, Engelhardt R. Effect of hyperthermia at 40.5 °C and chemotherapy on various human tumors in vitro. Recent Results Cancer Res. 1988;109:224–38.

    Article  CAS  PubMed  Google Scholar 

  82. Yamada K, et al. Predicting the sensitivity of human cancers to combined chemotherapy and hyperthermia. Recent Results Cancer Res. 1988;109:250–7.

    Article  CAS  PubMed  Google Scholar 

  83. Berger DP, et al. Cytotoxicity of TGF-alpha-PE40 and correlation to expression of epidermal growth factor receptor. Eur J Cancer. 1995;31:2067–72.

    Article  Google Scholar 

  84. Berger DP, et al. Vascular endothelial growth factor (VEGF) mRNA expression in human tumor models of different histologies. Ann Oncol. 1995;6:817–25.

    Article  CAS  PubMed  Google Scholar 

  85. Baumgarten AJ, Fiebig HH, Burger AM. Molecular analysis of xenograft models of human cancer cachexia—possibilities for therapeutic intervention. Cancer Genomics Proteomics. 2007;4:223–32.

    CAS  PubMed  Google Scholar 

  86. Smith V, Wirth GJ, Fiebig HH, Burger AM. Tissue microarrays of human tumor xenografts: characterization of proteins involved in migration an d angiogenesis for application in the development of targeted anticancer agents. Cancer Genomics Proteomics. 2008;5:263–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Schandelmaier K, et al. Expression of Hsp90 in a panel of human tumor explants and its relation to response to treatment with the Hsp90 inhibitor 17-AAG. Cancer Res. 2005;65(9):104.

    Google Scholar 

  88. Fiebig HH, et al. Combined in vitro/in vivo test procedure with human tumor xenografts for anticancer drug development. Strahlenther Onkol. 1989;165:22–52.

    Google Scholar 

  89. Eisenbrand G, et al. Drug design: nitrosoureas. IARC scientific publications. 1986. p. 281–94.

    Google Scholar 

  90. Fiebig HH, et al. Phase I clinical trial of Lobaplatin (D-19466) after intravenous bolus injection. Onkologie. 1994;17:142–8.

    Google Scholar 

  91. Fiebig HH, et al. In-vitro and in vivo evaluation of US-NCI compounds in human tumor xenografts. Cancer Treat Rev. 1990;17:109–17.

    Article  CAS  PubMed  Google Scholar 

  92. Berger DP, et al. Präklinische Prüfung von Hepsulfam, Ipomeanol, Oxantrazol, Penclomedin, Pyrazindiazohydroxid und Rapamycin auf antineoplastische Wirksamkeit. In: Zeller WJ, et al., editors. Germering: W. Zuckschwerdt; 1992. p. 167–84.

    Google Scholar 

  93. Hendriks HR, Berger DP, Fiebig HH. New anticancer drug development: interim results of the cooperative program between the Freiburg preclinical anticancer drug development group and the EORTC new drug development office. In: Arnold 3, Köpf-Maier P, Micheel B, editors. Immunodeficient animals: Models for cancer research. Contrib Oncol. 1996;51:108–14.

    Google Scholar 

  94. Boven E, et al. Phase II preclinical drug screening in human tumor xenografts: a European multicenter collaborative study. Cancer Res. 1992;52:5940–7.

    CAS  PubMed  Google Scholar 

  95. Langdon SP, et al. Preclinical Phase II studies in human tumor xenografts: a European multicenter follow-up study. Ann Oncol. 1994;5:415–22.

    Article  CAS  PubMed  Google Scholar 

  96. Hendriks HR, et al. Comparative antitumor activity of Vinblastine-isoleucinate and related vinca alkaloids in human xenografts. Eur J Cancer. 1992;28A:767–73.

    Article  CAS  PubMed  Google Scholar 

  97. Hendriks HR, et al. Preclinical antitumor activity and animal toxicology studies of rhizoxin, a novel tubulin interacting agent. Ann Oncol. 1992;3(9):755–63.

    Article  CAS  PubMed  Google Scholar 

  98. Hendriks HR, Pizao PE, Berger DP, et al. E09, a novel bioreductive alkylating indoloquinone with preferential solid tumor activity and lack of bone marrow toxicity in preclinical models. Eur J Cancer. 1993;29(6):897–906.

    Article  Google Scholar 

  99. Hendriks HR, et al. High antitumour activity of ET743 against human tumour xenografts from melanoma, non-small-cell lung and ovarian cancer. Ann Oncol. 1999;10:1233–40.

    Article  CAS  PubMed  Google Scholar 

  100. Fiebig HH, et al. Wirksamkeit von Mitomycin-C an 61 menschlichen, in der Nacktmaus wachsenden Tumoren. In: Nagel G, editor. München: W. Zuckschwerdt; 1986. vol. 28.

    Google Scholar 

  101. Berger DP, Winterhalter BR, Fiebig HH. Chemotherapy: conventional agents. In: Boven W, Winograd W, editors. The nude mouse in oncology research. Boca Raton: CRC Press; 1991. p. 165–84.

    Google Scholar 

  102. Berger DP, et al. Preclinical activity of Hepsulfam and Busulfan in solid human tumor xenografts and human bone marrow. Anti-Cancer Drugs. 1992;3:531–9.

    Article  CAS  PubMed  Google Scholar 

  103. Fiebig HH, Berger DP. Preclinical Phase II trials. In: Boven E, Winograd W, editors. The nude mouse in oncology research. Amsterdam: CRC Press; 1991. p. 317–26.

    Google Scholar 

  104. Fiebig HH, et al. Antitumor activity of Avastin in a panel of 100 patient derived tumor models in vivo in relation to proteomic biomarker profiles. Mol Cancer Ther. 2007:A28.

    Google Scholar 

  105. Fiebig HH, et al. Determination of a 35 gene signature predictive for the effectiveness of Bevacizumab. Mol Cancer Ther. 2007:B10.

    Google Scholar 

  106. Fiebig HH, Vuaroqueaux V, et al. Predictive gene signatures for Bevacizumab and Cetuximab as well as cytotoxic agents. Int J Clin Pharmacol Ther. 2012;50(1):70–1.

    Article  CAS  PubMed  Google Scholar 

  107. Vuaroqueaux V, et al. Identification of tumors responding to Bevacizumab by gene signature using a quantitative RT-PCR from FFPE tumors. Cancer Res. 2009;69(9):2567.

    Google Scholar 

  108. Promny I. Die Validierung der prädiktiven Marker für das Therapieansprechen auf Bevacizumab bei Patienten mit metastasiertem kolorektalen Karzinom. Med Thesis. University of Freiburg. 2011.

    Google Scholar 

  109. Khambata-Ford S, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007;25:3230–7.

    Article  CAS  PubMed  Google Scholar 

  110. Vuaroqueaux V, et al. Clinical validation of a gene expression based signature predicting response to Cetuximab treatment. In: 35th ESMO Congress, vol. 21. 2010.

    Google Scholar 

  111. Fiebig HH, et al. Gene signatures developed from patient tumor explants grown in nude mice to predict tumor response to 11 cytotoxic drugs. Cancer Genomics Proteomics. 2007;4:187–96.

    PubMed  Google Scholar 

  112. Korrat A, et al. Gene signature-based prediction of tumor response to cyclophosphamide. Cancer Genomics Proteomics. 2007;4:187–96.

    CAS  PubMed  Google Scholar 

  113. Hidalgo M, et al. A pilot clinical study of treatment guided by personalized tumor grafts in patients with advanced cancer. Mol Cancer Ther. 2011;10(8):1311–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Stebbing J, et al. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer. 2014;120(13):2006–15.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Pollack A. Seeking cures, patients enlist mice stand-ins. Cancer Discov. 2014:928–1013.

    Google Scholar 

  116. Scudellari M. My mighty mouse. Personal drug regimens based on xenograft mice harboring a single patient’s tumor still need to prove their true utility medicine. The Scientist. 2015. p. 29.

    Google Scholar 

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Acknowledgments

Numerous scientists and technicians have contributed over 35 years to the research summarized in this chapter. I thank mainly Dietmar Berger, Angelika Burger (deceased in 2011), Thomas Metz, Florian Schmidt, and Vincent Vuaroqueaux for their conceptional contributions. This research was supported by grants from the German Ministry of Research and Technology; the National Cancer Institute, Bethesda; and the NDDO of the EORTC and in recent years by a number of contracts form the European Community.

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  1. 4HF Biotec GmbH and Oncotest GmbH until Nov. 2015, Am Flughafen 12 - 14, D-79108, Freiburg, Germany

    Heinz-Herbert Fiebig

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Correspondence to Heinz-Herbert Fiebig .

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  1. University of California and AntiCancer Inc., San Diego, California, USA

    Robert M. Hoffman

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Fiebig, HH. (2017). Patient-Derived Xenograft Models for Human Cancer: The Freiburg Experience. In: Hoffman, R. (eds) Patient-Derived Mouse Models of Cancer . Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-57424-0_3

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