JCT  Vol.4 No.9 , November 2013
Evolution of Tumor Model: From Animal Model of Tumor to Tumor Model in Animal
ABSTRACT

Patient derived xenograft (PDX) is defined as a growth of patients’ tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure on the traditional animal model of cancer to evolve to PDX is that the traditional models have not delivered as expected and traditional models have not predicted clinical success. In spite of well above 50 drugs developed and approved for oncology over the last several decades, there remains a nirking paucity of clinical success as a reminder that this war on cancer riding on the animal model is far from won. In a backbreaking attempt to analyze the failure, the limitation of the “model” system appeared to be the most rational cause of this shortcoming. It was more of a failure to test a drug rather than a failure to make a drug that stunted our collective growth and success in cancer research. PDX is the product of this age-old failure and its fitness is currently tested in virtually all organ-type solid tumors. This review will present and appraise PDX model in the context of its evolution, its future promise, its limitations and more specifically, the current content of PDX in different solid tumors including breast, lung, colorectal, prostrate, GBM, pancreatic, hepatocellular carcinoma and melanoma.


Cite this paper
N. Dey, Y. Sun, B. Leyland-Jones and P. De, "Evolution of Tumor Model: From Animal Model of Tumor to Tumor Model in Animal," Journal of Cancer Therapy, Vol. 4 No. 9, 2013, pp. 1411-1425. doi: 10.4236/jct.2013.49168.
References
[1]   N. J. Vogelzang, et al., “Clinical Cancer Advances 2011: Annual Report on Progress against Cancer from the American Society of Clinical Oncology,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, Vol. 30, No. 1, 2012, pp. 88-109.

[2]   Y. Yarden and C. Caldes, “Basic Cancer Research Is Essential for the Success of Personalised Medicine,” European Journal of Cancer, Vol. 49, No. 12, 2013, pp. 2619-2620. http://dx.doi.org/ 10.1016/j.ejca.2013.04.020

[3]   J. S. de Bono and A. Ashworth, “Translating Cancer Research into Targeted Therapeutics,” Nature, Vol. 467, No. 7315, 2010, pp. 543-549. http://dx.doi.org/10.1038/nature09339

[4]   M. Kalia, “Personalized Oncology: Recent Advances and Future Challenges,” Metabolism: Clinical and Experimental, Vol. 62, No. Suppl 1, 2013, pp. S11-S14. http://dx.doi.org/10.1016/j.metabol.2012. 08.016

[5]   S. A. Williams, W. C. Anderson, M. T. Santaguida and S. J. Dylla, “Patient-Derived Xenografts, the Cancer Stem Cell Paradigm, and Cancer Pathobiology in the 21st Century,” Laboratory Investigation; A Journal of Technical Methods and Pathology, Vol. 93, No. 9, 2013, pp. 970-982.

[6]   E. R. Mardis, “Genome Sequencing and Cancer,” Current Opinion in Genetics & Development, Vol. 22, No. 3, 2012, pp. 245-250. http://dx.doi.org/10.1016/j.gde.2012.03.005

[7]   J. A. Baron, “Screening for Cancer with Molecular Markers: Progress Comes with Potential Problems,” Nature Reviews. Cancer, Vol. 12, No. 5, 2012, pp. 368-371. http://dx.doi.org/10.1038/nrc3260

[8]   A. Prat and C. M. Perou, “Deconstructing the Molecular Portraits of Breast Cancer,” Molecular Oncology, Vol. 5, No. 1, 2011, pp. 5-23. http://dx.doi.org/10.1016/j.molonc.2010.11.003

[9]   R. Fisher, L. Pusztai and C. Swanton, “Cancer Heterogeneity: Implications for Targeted Therapeutics,” British Journal of Cancer, Vol. 108, No. 3, 2013, pp. 479-485. http://dx.doi.org/ 10.1038/bjc.2012.581

[10]   M. J. Ellis and C. M. Perou, “The Genomic Landscape of Breast Cancer as a Therapeutic Roadmap,” Cancer Discovery, Vol. 3, No. 1, 2013, pp. 27-34.

[11]   Cancer Genome Atlas Network, “Comprehensive Molecular Portraits of Human Breast Tumours,” Nature, Vol. 490, No. 7418, 2012, pp. 61-70. http://dx.doi.org/10.1038/nature11412

[12]   M. F. Clarke, et al., “Cancer Stem Cells—Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells,” Cancer Research, Vol. 66, No. 19, 2006, pp. 9339-9344.
http://dx.doi.org/10.1158/0008-5472.CAN-06-3126

[13]   C. A. O’Brien, A. Kreso and C. H. Jamieson, “Cancer Stem Cells and Self-Renewal,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 16, No. 12, 2010, pp. 3113-3120.

[14]   P. Valent, et al., “Cancer Stem Cell Definitions and Terminology: The Devil Is in the Details,” Nature Reviews. Cancer, Vol. 12, No. 11, 2012, pp. 767-775. http://dx.doi.org/10.1038/nrc3368

[15]   J. A. DiMasi and H. G. Grabowski, “Economics of New Oncology Drug Development,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, Vol. 25, No. 2, 2007, pp. 209-216.

[16]   J. J. Tentler, et al., “Patient-Derived Tumour Xenografts as Models for Oncology Drug Development,” Nature Reviews. Clinical Oncology, Vol. 9, No. 6, 2012, pp. 338350.

[17]   T. Van Dyke, “Finding the Tumor Copycat: Approximating a Human Cancer,” Nature Medicine, Vol. 16, No. 9, 2010, pp. 976-977. http://dx.doi.org/10.1038/nm0910-976

[18]   J. M. Reichert and J. B. Wenger “Development Trends for New Cancer Therapeutics and Vaccines,” Drug Discovery Today, Vol. 13, No. 1-2, 2008, pp. 30-37. http://dx.doi.org/10.1016/j.drudis.2007. 09.003

[19]   L. M. Ellis and I. J. Fidler “Finding the Tumor Copycat. Therapy Fails, Patients Don’t,” Nature Medicine, Vol. 16, No. 9, 2010, pp. 974-975. http://dx.doi.org/10.1038/nm0910-974

[20]   D. Siolas and G. J. Hannon “Patient-Derived Tumor Xenografts: Transforming Clinical Samples into Mouse Models,” Cancer Research, Vol. 73, No. 17, 2013, pp. 5315-5319. http://dx.doi.org/10.1158/ 0008-5472.CAN-13-1069

[21]   K. Jin, et al., “Patient-Derived Human Tumour Tissue Xenografts in Immunodeficient Mice: A Systematic Review,” Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, Vol. 12, No. 7, 2010, pp. 473-480.

[22]   C. L. Morton and P. J. Houghton, “Establishment of Human Tumor Xenografts in Immunodeficient Mice,” Nature Protocols, Vol. 2, No. 2, 2007, pp. 247-250. http://dx.doi.org/10.1038/nprot.2007.25

[23]   D. Decaudin, “Primary Human Tumor Xenografted Models (Tumorgrafts) for Good Management of Patients with Cancer,” Anticancer Drugs, Vol. 22, No. 9, 2011, pp. 827-841. http://dx.doi.org/ 10.1097/CAD.0b013e3283475f70

[24]   F. Reyal, et al., “Molecular Profiling of Patient-Derived Breast Cancer Xenografts,” Breast Cancer Research: BCR, Vol. 14, No. 1, 2012, p. R11. http://dx.doi.org/10.1186/bcr3095

[25]   C. O. Povlsen, J. Visfeldt, J. Rygaard and G. Jensen, “Growth Patterns and Chromosome Constitutions of Human Malignant Tumours after Long-Term Serial Transplantation in Nude Mice,” Acta Pathologica et Microbiologica Scandinavica. Section A, Pathology, Vol. 83, No. 6, 1975, pp. 709-716.

[26]   S. Kopetz, R. Lemos and G. Powis, “The Promise of Patient-Derived Xenografts: The Best Laid Plans of Mice and Men,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 18, No. 19, 2012, pp. 5160-5162.

[27]   S. Li, et al., “Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts,” Cell Reports, Vol. 4, No. 6, 2013, pp. 1116-1130.

[28]   J. Mendelsohn, “Personalizing Oncology: Perspectives and Prospects,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, Vol. 31, No. 15, 2013, pp. 1904-1911.

[29]   Fiebig H-H & Burger AM (Human Tumor Xenografts and Explants, Springer, 2002.

[30]   A. Bertotti, et al., “A Molecularly Annotated Platform of Patient-Derived Xenografts (Xenopatients) Identifies HER2 as an Effective Therapeutic Target in CetuximabResistant Colorectal Cancer,” Cancer Discovery, Vol. 1, No. 6, 2011, pp. 508-523.

[31]   P. Kabos, et al., “Patient-Derived Luminal Breast Cancer Xenografts Retain Hormone Receptor Heterogeneity and Help Define Unique Estrogen-Dependent Gene Signatures,” Breast Cancer Research and Treatment, Vol. 135, No. 2, 2012, pp. 415-432. http://dx.doi.org/10.1007/s10549-012-2164-8

[32]   X. Zhang, et al., “A Renewable Tissue Resource of Phenotypically Stable, Biologically and Ethnically Diverse, Patient-Derived Human Breast Cancer Xenograft Models,” Cancer Research, Vol. 73, No. 15, 2013, pp. 4885-4897. http://dx.doi.org/10.1158/0008-5472.CAN-12-4081

[33]   R. S. Kerbel, “Human Tumor Xenografts as Predictive Preclinical Models for Anticancer Drug Activity in Humans: Better than Commonly Perceived, But They Can Be Improved,” Cancer Biology & Therapy, Vol. 2, No. 4, 2003, pp. S134-S139.

[34]   S. Oesterreich, A. M. Brufsky and N. E. Davidson, “Using Mice to Treat (Wo)men: Mining Genetic Changes in Patient Xenografts to Attack Breast Cancer,” Cell Reports, Vol. 4, No. 6, 2013, pp. 1061-1062.

[35]   D. J. Monsma, et al., “Genomic Characterization of Explant Tumorgraft Models Derived from Fresh Patient Tumor Tissue,” Journal of Translational Medicine, Vol. 10, No. 1, 2012, p. 125.
http://dx.doi.org/10.1186/1479-5876-10-125

[36]   M. Moro, G. Bertolini, M. Tortoreto, U. Pastorino, G. Sozzi and L. Roz, “Patient-Derived Xenografts of Non Small Cell Lung Cancer: Resurgence of an Old Model for Investigation of Modern Concepts of Tailored Therapy and Cancer Stem Cells,” Journal of Biomedicine & Bio-Technology, Vol. 2012, No. 2012, 2012, Article ID: 568567. http://dx.doi.org/10.1155/2012/568567

[37]   E. Marangoni, A. Vincent-Salomon, N. Auger, A. Degeorges, F. Assayag, P. de Cremoux, L. de Plater, C. Guyader, G. De Pinieux, J. G. Judde, M. Rebucci, C. Tran-Perennou, X. Sastre-Garau, B. Sigal-Zafrani, O. Delattre, V. Diéras and M. F. Poupon, “A New Model of Patient Tumor-Derived Breast Cancer Xenografts for Preclinical Assays,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 13, No. 13, 2007, pp. 3989-3998.

[38]   L. de Plater, A. Laugé, C. Guyader, M.-F. Poupon, F. Assayag, P. de Cremoux, A. Vincent-Salomon, D. Stoppa-Lyonnet, B. Sigal-Zafrani, J.-J. Fontaine, R. Brough, C. J. Lord, A. Ashworth, P. Cottu, D. Decaudin and E. Marangoni, “Establishment and Characterisation of a New Breast Cancer Xenograft Obtained from a Woman Carrying a Germline BRCA2 Mutation,” British Journal of Cancer, Vol. 103, No. 8, 2010, pp. 1192-1200. http://dx.doi.org/10.1038/sj.bjc.6605900

[39]   A. Romanelli, A. Clark, F. Assayag, S. Chateau-Joubert, M.-F. Poupon, J.-L. Servely, J.-J. Fontaine, X. H. Liu, E. Spooner, S. Goodstal, P. de Cremoux, I. Bièche, D. Decaudin and E. Marangon, “Inhibiting Aurora Kinases Reduces Tumor Growth and Suppresses Tumor Recurrence after Chemotherapy in Patient-Derived Triple-Negative Breast Cancer Xenografts,” Molecular Cancer Therapeutics, Vol. 11, No. 12, 2012, pp. 2693-2703. http://dx.doi.org/10.1158/1535-7163.MCT-12-0441-T

[40]   P. Cottu, E. Marangoni, F. Assayag, P. de Cremoux, A. Vincent-Salomon, Ch. Guyader, L. de Plater, C. Elbaz, N. Karboul, J. J. Fontaine, S. Chateau-Joubert, P. Boudou-Rouquette, S. Alran, V. Dangles-Marie, D. Gentien, M.-F. Poupon and D. Decaudin, “Modeling of Response to Endocrine Therapy in a Panel of Human Luminal Breast Cancer Xenografts,” Breast Cancer Research and Treatment, Vol. 133, No. 2, 2012, pp. 595-606. http://dx.doi.org/10.1007/s10549-011-1815-5

[41]   Y. S. DeRose, K. M. Gligorich, G. Wang, A. Georgelas, P. Bowman, S. J. Courdy, A. L. Welm, B. E. Welm, “Patient-Derived Models of Human Breast Cancer: Protocols for in Vitro and in Vivo Applications in Tumor Biology and Translational Medicine,” Current Protocols in Pharmacology, 2013, Chapter 14: Unit 14 23.

[42]   J. J. Wallin, J. Guan, W. W. Prior, L. B. Lee, L. Berry, L. D. Belmont, H. Koeppen, M. Belvin, L. S. Friedman, D. Sampath, “GDC-0941, a Novel Class I Selective PI3K Inhibitor, Enhances the Efficacy of Docetaxel in Human Breast Cancer Models by Increasing Cell Death in Vitro and in Vivo,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 18, No. 14, 2012, pp. 3901-3911.

[43]   C. Ginestier, S. L. Liu, M. E. Diebel, H. Korkaya, M. Luo, M. Brown, J. Wicinski, O. Cabaud, E. Charafe-Jauffret, D. Birnbaum, J.-L. Guan, G. Dontu and M. S. Wicha, “CXCR1 Blockade Selectively Targets Human Breast Cancer Stem Cells in Vitro and in Xenografts,” The Journal of Clinical Investigation, Vol. 120, No. 2, 2010, pp. 485-497. http://dx.doi.org/10.1172/JCI39397

[44]   T. John, D. Kohler, M. Pintilie, N. Yanagawa, N. A. Pham, M. Li, D. Panchal, F. Hui, F. Meng, F. A. Shepherd and M. S. Tsao, “The Ability to Form Primary Tumor Xenografts Is Predictive of Increased Risk of Disease Recurrence in Early-Stage Non-Small Cell Lung Cancer,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 17, No. 1, 2011, pp. 134-141.

[45]   Fichtner I, J. Rolff, R. Soong, J. Hoffmann, S. Hammer, A. Sommer, M. Becker and J. Merk, “Establishment of Patient-Derived Non-Small Cell Lung Cancer Xenografts as Models for the Identification of Predictive Biomarkers,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 14, No. 20, 2008, pp. 6456-6468.

[46]   X. Dong, J. Guan, J. C. English, J. Flint, J. Yee, K. Evans, N. Murray, C. Macaulay, R. T. Ng, P. W. Gout, W. L. Lam, J. Laskin, V. Ling, S. Lam and Y. Wang, “Patient-Derived First Generation Xenografts of Non-Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 16, No. 5 , 2010, pp. 1442-1451.

[47]   R. Krumbach, J. Schüler, M. Hofmann, T. Giesemann, H.-H. Fiebig and T. Beckers, “Primary Resistance to Cetuximab in a Panel of Patient-Derived Tumour Xenograft Models: Activation of MET as One Mechanism for Drug Resistance,” European Journal of Cancer, Vol. 47, No. 8, 2011, pp. 1231-1243. http://dx.doi.org/10.1016/j.ejca.2010.12.019

[48]   X. C. Zhang, J. C. Zhang, M. Li, X.-S. Huang, X.-N. Yang, W.-Z. Zhong, L. Xie, L. Zhang, M. H. Zhou, P. Gavine, X. Y. Su, L. Zheng, G. S. Zhu, P. Zhan, Q. S. Ji and Y.-L. Wu, “Establishment of Patient-Derived Non-Small Cell Lung Cancer Xenograft Models with Genetic Aberrations within EGFR, KRAS and FGFR1: Useful Tools for Preclinical Studies of Targeted Therapies,” Journal of Translational Medicine, Vol. 11, 2013, p. 168. http://dx.doi.org/10.1186/1479-5876-11-168

[49]   M. Yang, B. Shan, Q. Li, X. Song, J. Cai, J. Deng, L. Zhang, Z. Du, J. Lu, T. Chen, J. P. Wery, Y. Chen and Q. Li, “Overcoming Erlotinib Resistance with Tailored Treatment Regimen in Patient-Derived Xenografts from Naive Asian NSCLC Patients,” International Journal of Cancer, Vol. 132, No. 2, 2013, pp. E74-E84.

[50]   A. Bertotti, et al., “A Molecularly Annotated Platform of Patient-Derived Xenografts (‘Xenopatients’) Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer,” Cancer Discovery, Vol. 1, 2011, pp. 508-523. http://dx.doi.org/10.1158/2159-8290.CD-11-0109

[51]   S. Julien, et al., “Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 18, No. 19, 2012, pp. 5314-5328.

[52]   H. B. Zhu, W. Zhou, J. Z. Hu, Z. T. Huang, W. F. Lao, X. F. Huang and C. He, “Suppressing the Growth of Rectal Cancer Xenografts Derived from Patient Tumors by an Adenovector Expressing Small Hairpin RNA Targeting Bcl-XL,” The Journal of Gene Medicine, Vol. 14, No. 12, 2012. pp. 761-768. http://dx.doi.org/10.1002/jgm.2681

[53]   R. Toivanen, R. A. Taylor, D. W. Pook, S. J. Ellem and G. P. Risbridger, “Breaking through a Roadblock in Prostate Cancer Research: An Update on Human Model Systems,” The Journal of Steroid Biochemistry and Molecular Biology, Vol. 131, No. 3-5, 2012, pp. 122-131. http://dx.doi.org/ 10.1016/j.jsbmb.2012.01.005

[54]   O. Raheem, A. A. Kulidjian, C. Wu, Y. B. Jeong, T. Yamaguchi, K. M. Smith, D. Goff, H. Leu, S. R. Morris, N. A Cacalano, K. Masuda, C. H. M. Jamieson, C. J. Kane and C. A. M. Jamieson, “A Novel Patient-Derived Intra-Femoral Xenograft Model of Bone Metastatic Prostate Cancer that Recapitulates Mixed Osteolytic and Osteoblastic Lesions,” Journal of Translational Medicine, Vol. 9, 2011, p. 185. http://dx.doi.org/10.1186/1479-5876-9-185

[55]   A. Aparicio, V. Tzelepi, J. C. Araujo, C. C. Guo, S. D. Liang, P. Troncoso, C. J. Logothetis, N. M. Navone and S. N. Maity, “Neuroendocrine Prostate Cancer Xenografts with Large-Cell and Small-Cell Features Derived from a Single Patient’s Tumor: Morphological, Immunohistochemical, and Gene Expression Profiles,” The Prostate, Vol. 71, No. 8, 2011, pp. 846-856. http://dx.doi.org/ 10.1002/pros.21301

[56]   T. Kimura, H. Kiyota1, D. Nakata, T. Masaki, Masami Kusaka and S. Egawa, “A Novel Androgen-Dependent Prostate Cancer Xenograft Model Derived from Skin Metastasis of a Japanese Patient,” The Prostate, Vol. 69, No. 15, 2009, pp. 1660-1667. http://dx.doi.org/10.1002/pros.21016

[57]   T. Yoshida, H. Kinoshita, T. Segawa, E. Nakamura, T. Inoue, Y. Shimizu, T. Kamoto and O. Ogawa, “Antiandrogen Bicalutamide Promotes Tumor Growth in a Novel Androgen-Dependent Prostate Cancer Xenograft Model Derived from a Bicalutamide-Treated Patient,” Cancer Research, Vol. 65, No. 21, 2005, pp. 9611-9616. http://dx.doi.org/10.1158/0008-5472.CAN-05-0817

[58]   X. S. Li, Z. B. Liu, X. Xu, C. A. Blair, Z. Sun, J. Xie, M. B. lilly and X. L. Zi, “Kava Components Down-Regulate Expression of AR and AR Splice Variants and Reduce Growth in Patient-Derived Prostate Cancer Xenografts in Mice,” PLoS ONE, Vol. 7, No. 2, 2012, Article ID: e31213. http://dx.doi.org/ 10.1371/journal.pone.0031213

[59]   S. E. Yost, S. Pastorino, S. Rozenzhak, E. N. Smith, Y. S. Chao, P. F. Jiang, S. Kesari, K. A. Frazer and O. Harismendy, “High-Resolution Mutational Profiling Suggests the Genetic Validity of Glioblastoma Patient-Derived Pre-Clinical Models,” PLoS ONE, Vol. 8, No. 2, 2013, Article ID: e56185. http://dx.doi.org/10.1371/journal.pone.0056185

[60]   M. A. Jarzabek, P. C. Huszthy, K. O. Skaftnesmo, E. McCormack, P. Dicker, J. H.M. Prehn, R. Bjerkvig and A. T. Byrne, “In Vivo Bioluminescence Imaging Validation of a Human Biopsy-Derived Orthotopic Mouse Model of Glioblastoma Multiforme,” Molecular Imaging, Vol. 12, No. 3, 2013, pp. 161-172.

[61]   K. H. Kim, H. J. Seol, E. H. Kim, J. Rheey, H. J. Jin, Y. Lee, K. M. Joo, J. Lee and D.-H. Nam, “Wnt/Beta-Catenin Signaling Is a Key Downstream Mediator of MET Signaling in Glioblastoma Stem Cells,” Neuro-Oncology, Vol. 15, No. 2, 2013, pp. 161-171. http://dx.doi.org/10.1093/neuonc/nos299

[62]   H. Huynh, K. C. Soo, P. K. Chow, L. Panasci and E. Tran, “Xenografts of Human Hepatocellular Carcinoma: A Useful Model for Testing Drugs,” Clinical Cancer Research, Vol. 12, 2006, pp. 4306-4314. http://dx.doi.org/10.1158/1078-0432.CCR-05-2568

[63]   M. Yan, H. Li, F. Y. Zhao, L. X. Zhang, C. Ge, M. Yao, and J. J. Li, “Establishment of NOD/SCID Mouse Models of Human Hepatocellular Carcinoma via Subcutaneous Transplantation of Histologically Intact Tumor Tissue,” Chinese Journal of Cancer Research, Vol. 25, No. 3, 2013, pp. 289-298.

[64]   H. Huynh, V. C. Ngo, H. N. Koong, D. Poon, S. P. Choo, H. C. Toh, C. H. Thng, P. Chow, H. S. Ong, A. Chung, B. C. Goh, P. D. Smith and K. C. Soo, “AZD6244 Enhances the Anti-Tumor Activity of Sorafenib in Ectopic and Orthotopic Models of Human Hepatocellular Carcinoma (HCC),” Journal of Hepatology, Vol. 52, No. 1, 2010, pp. 79-87. http://dx.doi.org/10.1016/j.jhep.2009.10.008

[65]   H. Huynh, V. C. Ngo, J. Fargnoli, M. Ayers, K. C. Soo, H. N. Koong, C. H. Thng, H. S. Ong, A. Chung, P. Chow, P. Pollock, S. Byron and E. Tran, “Brivanib Alaninate, a Dual Inhibitor of Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Tyrosine Kinases, Induces Growth Inhibition in Mouse Models of Human Hepatocellular Carcinoma,” Clinical Cancer Research, Vol. 14, 2008, pp. 6146-6153. http://dx.doi.org/10.1158/1078-0432.CCR-08-0509

[66]   H. Huynh, V. C. Ngo, S. P. Choo, D. Poon, H. N. Koong, C. H. Thng, H. C. Toh, L. Zheng, L. C. Ong, Y. Jin, I. C. Song, A. P.C. Chang, H. S. Ong, A. Y.F. Chung, P. K.H. Chow and K. C. Soo, “Sunitinib (SUTENT, SU11248) Suppresses Tumor Growth and Induces Apoptosis in Xenograft Models of Human Hepatocellular Carcinoma,” Current Cancer Drug Targets, Vol. 9, No. 6, 2009, pp. 738-747. http://dx.doi.org/10.2174/156800909789271530

[67]   H. Huynh, K. H. P. Chow, K. C. Soo, H. C. Toh, S. P. Choo, K. F. Foo, D. Poon, V, C. Ngo and E. Tran, “RAD001 (Everolimus) Inhibits Tumour Growth in Xenograft Models of Human Hepatocellular Carcinoma,” Journal of Cellular and Molecular Medicine, Vol. 13, No. 7, 2009, pp. 1371-1380. http://dx.doi.org/10.1111/j.1582-4934.2008.00364.x

[68]   C. Krepler, V. Wacheck, S. Strommer, G. Hartmann, P. Polterauer, K. Wolff, H. Pehamberger and B. Jansen, “CpG Oligonucleotides Elicit Antitumor Responses in a Human Melanoma NOD/SCID Xenotransplantation Model,” The Journal of Investigative Dermatology, Vol. 122, No. 2, 2004, pp. 387-391. http://dx.doi.org/10.1046/j.0022-202X.2004.22202.x

[69]   J. M. Pimiento, E. M. Larkin, K. S. M. Smalley, G. L. Wiersma, N. R. Monks, I. V. Fedorenko, C. A. Peterson and B. J. Nickoloff, “Melanoma Genotypes and Phenotypes Get Personal,” Laboratory Investigation, Vol. 93, No. 8, 2013, pp. 858-867.

[70]   P. Guerreschi, C. Scalbert, A. Qassemyar, J. Kluza, L. Ravasi, D. Huglo, V. Martinot-Duquennoy, P. Formstecher, P. Marchetti and L. Mortier, “Patient-Derived Tumor Xenograft Model to Guide the Use of BRAF Inhibitors in Metastatic Melanoma,” Melanoma Research, Vol. 23, No. 5, 2013, pp. 373-380. http://dx.doi.org/10.1097/CMR.0b013e328363ed92

[71]   C. Laurent, D. Gentien, S. Piperno-Neumann, F. Némati, A. Nicolas, B. Tesson, L. Desjardins, P. Mariani, A. Rapinat, X. Sastre-Garau, J. Couturier, P. Hupé, L. de Koning, T. Dubois, S. Roman-Roman, M. H. Stern, E. Barillot, J. W. Harbour, S. Saule and D. Decaudin, “Patient-Derived Xenografts Recapitulate Molecular Features of Human Uveal Melanomas,” Molecular Oncology, Vol. 7, No. 3, 2013, pp. 625-636. http://dx.doi.org/10.1016/j.molonc.2013.02.004

[72]   F. Nemati, X. Sastre-Garau, C. Laurent, J. Couturier, P. Mariani, L. Desjardins, S. Piperno-Neumann, O. Lantz, B. Asselain, C. Plancher, D. Robert, I. Péguillet, M. H. Donnadieu, A. Dahmani, M. A. Bessard, D. Gentien, C. Reyes, S. Saule, E. Barillot, S. Roman-Roman and D. Decaudin, “Establishment and Characterization of a Panel of Human Uveal Melanoma Xenografts Derived from Primary and/or Metastatic Tumors,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 16, No. 8, 2010, pp. 2352-2362.

[73]   P. C. Gach, P. J. Attayek, G. Herrera, J. J. Yeh and N. L. Allbritton, “Isolation and in Vitro Culture of Rare Cancer Stem Cells from Patient-Derived Xenografts of Pancreatic Ductal Adenocarcinoma,” Analytical Chemistry, Vol. 85, No. 15, 2013, pp. 7271-7278. http://dx.doi.org/10.1021/ac401165s

[74]   D. M. Walters, J. M. Lindberg, S. J. Adair, T. E. Newhook, C. R. Cowan, J. B. Stokes, C. A. Borgman, E. B. Stelow, B. T. Lowrey, M. E. Chopivsky, T. M. Gilmer, J. T. Parsons and T. W. Bauer, “Inhibition of the Growth of Patient-Derived Pancreatic Cancer Xenografts with the MEK Inhibitor Trametinib Is Augmented by Combined Treatment with the Epidermal Growth Factor Receptor/ HER2 Inhibitor Lapatinib,” Neoplasia, Vol. 15, No. 2, 2013, pp. 143-155.

[75]   N. V. Rajeshkumar, Z. A. Rasheed, E. García-García, F. López-Ríos, K. Fujiwara, W. H. Matsui1 and M. Hidalgo, “A Combination of DR5 Agonistic Monoclonal Antibody with Gemcitabine Targets Pancreatic Cancer Stem Cells and Results in Long-Term Disease Control in Human Pancreatic Cancer Model,” Molecular Cancer Therapeutics, Vol. 9, No. 9, 2010, pp. 2582-2592. http://dx.doi.org/10.1158/1535-7163.MCT-10-0370

[76]   M. P. Kim, M. J. Truty, W. Choi, Y. Kang, X. Chopin-Lally, G. E. Gallick, H. Wang, D. J. McConkey, R. Hwang, C. Logsdon, J. Abbruzzesse and J. B. Fleming, “Molecular Profiling of Direct Xenograft Tumors Established from Human Pancreatic Adenocarcinoma after Neoadjuvant Therapy,” Annals of Surgical Oncology, Vol. 19, No. Suppl. 3, 2012, pp. 395-403. http://dx.doi.org/10.1245/s10434-011-1839-4

[77]   P. C. Hermann, et al., “Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts,” PLoS ONE, Vol. 8, No. 6, 2013, Article ID: e66371. http://dx.doi.org/10.1371/journal.pone.0066371

[78]   A. Jimeno, G. Feldmann, A Suárez-Gauthier, Z. Rasheed, A. Solomon1, G.-M. Zou, B. Rubio-Viqueira, E. García-García, F. López-Ríos, W. Matsui, A. Maitra1 and M. Hidalgo, “A Direct Pancreatic Cancer Xenograft Model as a Platform for Cancer Stem Cell Therapeutic Development,” Molecular Cancer Therapeutics, Vol. 8, No. 2, 2009, pp. 310-314. http://dx.doi.org/10.1158/1535-7163.MCT-08-0924

[79]   T. Hoey, W.-C. Yen, F. Axelrod, J. Basi, L. Donigian, S. Dylla, M. Fitch-Bruhns, S. Lazetic, I.-K. Park, A. Sato, S. Satyal, X. H. Wang, M. F. Clarke, J. Lewicki and A. Gurney, “DLL4 Blockade Inhibits Tumor Growth and Reduces Tumor-Initiating Cell Frequency,” Cell Stem Cell, Vol. 5, No. 2, 2009, pp. 168-177. http://dx.doi.org/10.1016/j.stem.2009.05.019

 
 
Top