Patient-derived xenograft models: an emerging platform for translational cancer research

. 2014 Sep ; 4 (9) : 998-1013. [epub] 20140715

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid25185190

Grantová podpora
16942 Cancer Research UK - United Kingdom
17263 Cancer Research UK - United Kingdom
A9401 Cancer Research UK - United Kingdom

Odkazy

PubMed 25185190
PubMed Central PMC4167608
DOI 10.1158/2159-8290.cd-14-0001
PII: 2159-8290.CD-14-0001
Knihovny.cz E-zdroje

UNLABELLED: Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biologic studies, and personalized medicine strategies. This article summarizes the current state of the art in this field, including methodologic issues, available collections, practical applications, challenges and shortcomings, and future directions, and introduces a European consortium of PDX models. SIGNIFICANCE: PDX models are increasingly used in translational cancer research. These models are useful for drug screening, biomarker development, and the preclinical evaluation of personalized medicine strategies. This review provides a timely overview of the key characteristics of PDX models and a detailed discussion of future directions in the field.

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Boyd M. The NCI in vitro antitumor drug discovery screen: concept, implementation, and operation, 1985-1995. In: Teicher B, editor. Anticancer Drug Development Guide: preclinical screening, Clinical Trials and Approval. Humana Press; Totowa: 1997.

Venditti JM, Wesley RA, Plowman J. Current NCI preclinical antitumor screening in vivo: results of tumor panel screening, 1976-1982, and future directions. Adv Pharmacol Chemother. 1984;20:1–20. PubMed

Abaan OD, Polley EC, Davis SR, Zhu YJ, Bilke S, Walker RL, et al. The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology. Cancer Res. 2013;73:4372–82. PubMed PMC

Johnson JI, Decker S, Zaharevitz D, Rubinstein LV, Venditti JM, Schepartz S, et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer. 2001;84:1424–31. PubMed PMC

Gillet JP, Calcagno AM, Varma S, Marino M, Green LJ, Vora MI, et al. Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance. Proc Natl Acad Sci U S A. 2011;108:18708–13. PubMed PMC

Hausser HJ, Brenner RE. Phenotypic instability of Saos-2 cells in long-term culture. Biochem Biophys Res Commun. 2005;333:216–22. PubMed

Fiebig HH, Neumann HA, Henss H, Koch H, Kaiser D, Arnold H. Development of three human small cell lung cancer models in nude mice. Recent Results Cancer Res. 1985;97:77–86. PubMed

Houghton JA, Houghton PJ, Green AA. Chemotherapy of childhood rhabdomyosarcomas growing as xenografts in immune-deprived mice. Cancer Res. 1982;42:535–9. PubMed

Berger DP, Fiebig HH, Winterhalter BR, Wallbrecher E, Henss H. Preclinical phase II study of ifosfamide in human tumour xenografts in vivo. Cancer Chemother Pharmacol. 1990;26(Suppl):S7–11. PubMed

Calles A, Rubio-Viqueira B, Hidalgo M. Primary human non-small cell lung and pancreatic tumorgraft models--utility and applications in drug discovery and tumor biology. Curr Protoc Pharmacol. 2013 Chapter 14:Unit 14 26. PubMed

Siolas D, Hannon GJ. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 2013;73:5315–9. PubMed PMC

Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol. 2012;9:338–50. PubMed PMC

Kim MP, Evans DB, Wang H, Abbruzzese JL, Fleming JB, Gallick GE. Generation of orthotopic and heterotopic human pancreatic cancer xenografts in immunodeficient mice. Nat Protoc. 2009;4:1670–80. PubMed PMC

Nemati F, Sastre-Garau X, Laurent C, Couturier J, Mariani P, Desjardins L, et al. Establishment and characterization of a panel of human uveal melanoma xenografts derived from primary and/or metastatic tumors. Clin Cancer Res. 2010;16:2352–62. PubMed

Sivanand S, Pena-Llopis S, Zhao H, Kucejova B, Spence P, Pavia-Jimenez A, et al. A validated tumorgraft model reveals activity of dovitinib against renal cell carcinoma. Sci Transl Med. 2012;4:137ra75. PubMed PMC

Zhang X, Claerhout S, Prat A, Dobrolecki LE, Petrovic I, Lai Q, et al. A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models. Cancer Res. 2013;73:4885–97. PubMed PMC

Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67. PubMed PMC

Vidal A, Munoz C, Guillen MJ, Moreto J, Puertas S, Martinez-Iniesta M, et al. Lurbinectedin (PM01183), a new DNA minor groove binder, inhibits growth of orthotopic primary graft of cisplatin-resistant epithelial ovarian cancer. Clin Cancer Res. 2012;18:5399–411. PubMed

Wang X, Fu X, Hoffman RM. A new patient-like metastatic model of human lung cancer constructed orthotopically with intact tissue via thoracotomy in immunodeficient mice. Int J Cancer. 1992;51:992–5. PubMed

Dong X, Guan J, English JC, Flint J, Yee J, Evans K, et al. Patient-derived first generation xenografts of non-small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy. Clin Cancer Res. 2010;16:1442–51. PubMed

Fichtner I, Rolff J, Soong R, Hoffmann J, Hammer S, Sommer A, et al. Establishment of patient-derived non-small cell lung cancer xenografts as models for the identification of predictive biomarkers. Clin Cancer Res. 2008;14:6456–68. PubMed

Li S, Shen D, Shao J, Crowder R, Liu W, Prat A, et al. Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Rep. 2013;4:1116–30. PubMed PMC

Kresse SH, Meza-Zepeda LA, Machado I, Llombart-Bosch A, Myklebost O. Preclinical xenograft models of human sarcoma show nonrandom loss of aberrations. Cancer. 2012;118:558–70. PubMed

Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature. 2010;464:999–1005. PubMed PMC

Keysar SB, Astling DP, Anderson RT, Vogler BW, Bowles DW, Morton JJ, et al. A patient tumor transplant model of squamous cell cancer identifies PI3K inhibitors as candidate therapeutics in defined molecular bins. Mol Oncol. 2013;7:776–90. PubMed PMC

Rubio-Viqueira B, Jimeno A, Cusatis G, Zhang X, Iacobuzio-Donahue C, Karikari C, et al. An in vivo platform for translational drug development in pancreatic cancer. Clin Cancer Res. 2006;12:4652–61. PubMed

Daniel VC, Marchionni L, Hierman JS, Rhodes JT, Devereux WL, Rudin CM, et al. A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res. 2009;69:3364–73. PubMed PMC

Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C, et al. A molecularly annotated platform of patient-derived xenografts (“xenopatients”) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2011;1:508–23. PubMed

Julien S, Merino-Trigo A, Lacroix L, Pocard M, Goere D, Mariani P, et al. Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin Cancer Res. 2012;18:5314–28. PubMed

DeRose YS, Wang G, Lin YC, Bernard PS, Buys SS, Ebbert MT, et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med. 2011;17:1514–20. PubMed PMC

Reyal F, Guyader C, Decraene C, Lucchesi C, Auger N, Assayag F, et al. Molecular profiling of patient-derived breast cancer xenografts. Breast Cancer Res. 2012;14:R11. PubMed PMC

Moestue SA, Borgan E, Huuse EM, Lindholm EM, Sitter B, Borresen-Dale AL, et al. Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models. BMC Cancer. 2010;10:433. PubMed PMC

Garrido-Laguna I, Uson M, Rajeshkumar NV, Tan AC, de Oliveira E, Karikari C, et al. Tumor engraftment in nude mice and enrichment in stroma-related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer. Clin Cancer Res. 2011;17:5793–800. PubMed PMC

Marangoni E, Vincent-Salomon A, Auger N, Degeorges A, Assayag F, de Cremoux P, et al. A new model of patient tumor-derived breast cancer xenografts for preclinical assays. Clin Cancer Res. 2007;13:3989–98. PubMed

Hidalgo M, Bruckheimer E, Rajeshkumar NV, Garrido-Laguna I, De Oliveira E, Rubio-Viqueira B, et al. A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer. Mol Cancer Ther. 2011;10:1311–6. PubMed PMC

Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov. 2004;3:711–5. PubMed

Migliardi G, Sassi F, Torti D, Galimi F, Zanella ER, Buscarino M, et al. Inhibition of MEK and PI3K/mTOR suppresses tumor growth but does not cause tumor regression in patient-derived xenografts of RAS-mutant colorectal carcinomas. Clin Cancer Res. 2012;18:2515–25. PubMed

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703. PubMed PMC

Garrido-Laguna I, Tan AC, Uson M, Angenendt M, Ma WW, Villaroel MC, et al. Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer. Br J Cancer. 2010;103:649–55. PubMed PMC

Rajeshkumar NV, Tan AC, De Oliveira E, Womack C, Wombwell H, Morgan S, et al. Antitumor effects and biomarkers of activity of AZD0530, a Src inhibitor, in pancreatic cancer. Clin Cancer Res. 2009;15:4138–46. PubMed

Sebastiani V, Ricci F, Rubio-Viqueira B, Kulesza P, Yeo CJ, Hidalgo M, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res. 2006;12:2492–7. PubMed PMC

Moestue S, Sitter B, Bathen TF, Tessem MB, Gribbestad IS. HR MAS MR spectroscopy in metabolic characterization of cancer. Curr Top Med Chem. 2011;11:2–26. PubMed

Moestue SA, Huuse EM, Lindholm EM, Bofin A, Engebraaten O, Maelandsmo GM, et al. Low-molecular contrast agent dynamic contrast-enhanced (DCE)-MRI and diffusion-weighted (DW)-MRI in early assessment of bevacizumab treatment in breast cancer xenografts. J Magn Reson Imaging. 2013;38:1043–53. PubMed

Bardelli A, Corso S, Bertotti A, Hobor S, Valtorta E, Siravegna G, et al. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov. 2013;3:658–73. PubMed PMC

Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature. 2013;494:251–5. PubMed PMC

Anido J, Saez-Borderias A, Gonzalez-Junca A, Rodon L, Folch G, Carmona MA, et al. TGF-beta Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma. Cancer Cell. 2010;18:655–68. PubMed

Lonardo E, Hermann PC, Mueller MT, Huber S, Balic A, Miranda-Lorenzo I, et al. Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell. 2011;9:433–46. PubMed

Mueller MT, Hermann PC, Witthauer J, Rubio-Viqueira B, Leicht SF, Huber S, et al. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology. 2009;137:1102–13. PubMed

Yen WC, Fischer MM, Hynes M, Wu J, Kim E, Beviglia L, et al. Anti-DLL4 has broad spectrum activity in pancreatic cancer dependent on targeting DLL4-Notch signaling in both tumor and vasculature cells. Clin Cancer Res. 2012;18:5374–86. PubMed

Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501:346–54. PubMed

Chen Z, Cheng K, Walton Z, Wang Y, Ebi H, Shimamura T, et al. A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response. Nature. 2012;483:613–7. PubMed PMC

Nardella C, Lunardi A, Patnaik A, Cantley LC, Pandolfi PP. The APL paradigm and the “co-clinical trial” project. Cancer Discov. 2011;1:108–16. PubMed PMC

Jimeno A, Amador ML, Kulesza P, Wang X, Rubio-Viqueira B, Zhang X, et al. Assessment of celecoxib pharmacodynamics in pancreatic cancer. Mol Cancer Ther. 2006;5:3240–7. PubMed

Dancey JE, Bedard PL, Onetto N, Hudson TJ. The genetic basis for cancer treatment decisions. Cell. 2012;148:409–20. PubMed

Garraway LA. Genomics-driven oncology: framework for an emerging paradigm. J Clin Oncol. 2013;31:1806–14. PubMed

Diaz LA, Jr., Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 2012;486:537–40. PubMed PMC

Garber K. Personal mouse colonies give hope for pancreatic cancer patients. J Natl Cancer Inst. 2007;99:105–7. PubMed

Valencia A, Hidalgo M. Getting personalized cancer genome analysis into the clinic: the challenges in bioinformatics. Genome Med. 2012;4:61. PubMed PMC

Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483:603–7. PubMed PMC

De Wever O, Mareel M. Role of tissue stroma in cancer cell invasion. J Pathol. 2003;200:429–47. PubMed

Kleine W. Prognostic significance of growth characteristics of xenotransplanted ovarian carcinomas into nude mice. Gynecol Oncol. 1986;25:65–72. PubMed

Kondo J, Endo H, Okuyama H, Ishikawa O, Iishi H, Tsujii M, et al. Retaining cell-cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. Proc Natl Acad Sci U S A. 2011;108:6235–40. PubMed PMC

Weiswald LB, Richon S, Validire P, Briffod M, Lai-Kuen R, Cordelieres FP, et al. Newly characterised ex vivo colospheres as a three-dimensional colon cancer cell model of tumour aggressiveness. Br J Cancer. 2009;101:473–82. PubMed PMC

Dalerba P, Kalisky T, Sahoo D, Rajendran PS, Rothenberg ME, Leyrat AA, et al. Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat Biotechnol. 2011;29:1120–7. PubMed PMC

Kamiyama H, Rauenzahn S, Shim JS, Karikari CA, Feldmann G, Hua L, et al. Personalized chemotherapy profiling using cancer cell lines from selectable mice. Clin Cancer Res. 2013;19:1139–46. PubMed PMC

Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883–92. PubMed PMC

Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 2012;486:395–9. PubMed PMC

Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467:1114–7. PubMed PMC

Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol. 2013;31:539–44. PubMed

Embuscado EE, Laheru D, Ricci F, Yun KJ, de Boom Witzel S, Seigel A, et al. Immortalizing the complexity of cancer metastasis: genetic features of lethal metastatic pancreatic cancer obtained from rapid autopsy. Cancer Biol Ther. 2005;4:548–54. PubMed PMC

Kalscheuer H, Danzl N, Onoe T, Faust T, Winchester R, Goland R, et al. A model for personalized in vivo analysis of human immune responsiveness. Sci Transl Med. 2012;4:125ra30. PubMed PMC

van der Meel R, Gallagher WM, Oliveira S, O’Connor AE, Schiffelers RM, Byrne AT. Recent advances in molecular imaging biomarkers in cancer: application of bench to bedside technologies. Drug Discov Today. 2010;15:102–14. PubMed

O’Neill K, Lyons SK, Gallagher WM, Curran KM, Byrne AT. Bioluminescent imaging: a critical tool in pre-clinical oncology research. J Pathol. 2010;220:317–27. PubMed

Welm BE, Dijkgraaf GJ, Bledau AS, Welm AL, Werb Z. Lentiviral transduction of mammary stem cells for analysis of gene function during development and cancer. Cell Stem Cell. 2008;2:90–102. PubMed PMC

Yuan Y, Failmezger H, Rueda OM, Ali HR, Graf S, Chin SF, et al. Quantitative image analysis of cellular heterogeneity in breast tumors complements genomic profiling. Sci Transl Med. 2012;4:157ra43. PubMed

Aytes A, Mollevi DG, Martinez-Iniesta M, Nadal M, Vidal A, Morales A, et al. Stromal interaction molecule 2 (STIM2) is frequently overexpressed in colorectal tumors and confers a tumor cell growth suppressor phenotype. Mol Carcinog. 2012;51:746–53. PubMed

Reyes G, Villanueva A, Garcia C, Sancho FJ, Piulats J, Lluis F, et al. Orthotopic xenografts of human pancreatic carcinomas acquire genetic aberrations during dissemination in nude mice. Cancer Res. 1996;56:5713–9. PubMed

Kimple RJ, Harari PM, Torres AD, Yang RZ, Soriano BJ, Yu M, et al. Development and characterization of HPV-positive and HPV-negative head and neck squamous cell carcinoma tumorgrafts. Clin Cancer Res. 2013;19:855–64. PubMed PMC

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