Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Review

Current status and perspectives of patient-derived xenograft models in cancer research

Authors: Yunxin Lai, Xinru Wei, Shouheng Lin, Le Qin, Lin Cheng, Peng Li

Published in: Journal of Hematology & Oncology | Issue 1/2017

Login to get access

Abstract

Cancers remain a major public health problem worldwide, which still require profound research in both the basic and preclinical fields. Patient-derived xenograft (PDX) models are created when cancerous cells or tissues from patients’ primary tumors are implanted into immunodeficient mice to simulate human tumor biology in vivo, which have been extensively used in cancer research. The routes of implantation appeared to affect the outcome of PDX research, and there has been increasing applications of patient-derived orthotopic xenograft (PDOX) models. In this review, we firstly summarize the methodology to establish PDX models and then go over recent application and function of PDX models in basic cancer research on the areas of cancer characterization, initiation, proliferation, metastasis, and tumor microenvironment and in preclinical explorations of anti-cancer targets, drugs, and therapeutic strategies and finally give our perspectives on the future prospects of PDX models.
Literature
1.
Singer DS, Jacks T, Jaffee E, A U.S. “Cancer Moonshot” to accelerate cancer research. Science. 2016;353:1105–6.PubMedCrossRef
2.
Siegel RL, Miller KD, Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.
3.
Chen C, He M, Zhu Y, Shi L, Wang X. Five critical elements to ensure the precision medicine. Cancer Metastasis Rev. 2015;34:313–8.PubMedCrossRef
4.
Hoffman RM. Patient-derived orthotopic xenografts: better mimic of metastasis than subcutaneous xenografts. Nat Rev Cancer. 2015;15:451–2.PubMedCrossRef
5.
Durig J, Ebeling P, Grabellus F, Sorg UR, Mollmann M, Schutt P, Gothert J, Sellmann L, Seeber S, Flasshove M, et al. A novel nonobese diabetic/severe combined immunodeficient xenograft model for chronic lymphocytic leukemia reflects important clinical characteristics of the disease. Cancer Res. 2007;67:8653–61.PubMedCrossRef
6.
Chapuy B, Cheng H, Watahiki A, Ducar MD, Tan Y, Chen L, Roemer MG, Ouyang J, Christie AL, Zhang L, et al. Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biological heterogeneity of the disease. Blood. 2016;127:2203–13.PubMedPubMedCentralCrossRef
7.
Tignanelli CJ, Herrera Loeza SG, Yeh JJ. KRAS and PIK3CA mutation frequencies in patient-derived xenograft models of pancreatic and colorectal cancer are reflective of patient tumors and stable across passages. Am Surg. 2014;80:873–7.PubMedPubMedCentral
8.
Seol HS, Kang HJ, Lee SI, Kim NE, Kim TI, Chun SM, Kim TW, Yu CS, Suh YA, Singh SR, et al. Development and characterization of a colon PDX model that reproduces drug responsiveness and the mutation profiles of its original tumor. Cancer Lett. 2014;345:56–64.PubMedCrossRef
9.
Zhu Y, Tian T, Li Z, Tang Z, Wang L, Wu J, Li Y, Dong B, Li Y, Li N, et al. Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer. Sci Rep. 2015;5:8542.PubMedPubMedCentralCrossRef
10.
Zhang T, Zhang L, Fan S, Zhang M, Fu H, Liu Y, Yin X, Chen H, Xie L, Zhang J, et al. Patient-derived gastric carcinoma xenograft mouse models faithfully represent human tumor molecular diversity. PLoS One. 2015;10:e0134493.PubMedPubMedCentralCrossRef
11.
Dong R, Qiang W, Guo H, Xu X, Kim JJ, Mazar A, Kong B, Wei JJ. Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma. J Hematol Oncol. 2016;9:92.PubMedPubMedCentralCrossRef
12.
Cavalloni G, Peraldo-Neia C, Sassi F, Chiorino G, Sarotto I, Aglietta M, Leone F. Establishment of a patient-derived intrahepatic cholangiocarcinoma xenograft model with KRAS mutation. BMC Cancer. 2016;16:90.PubMedPubMedCentralCrossRef
13.
Kuracha MR, Thomas P, Loggie BW, Govindarajan V. Patient-derived xenograft mouse models of pseudomyxoma peritonei recapitulate the human inflammatory tumor microenvironment. Cancer Med. 2016;5:711–9.PubMedPubMedCentralCrossRef
14.
Morton CL, Houghton PJ. Establishment of human tumor xenografts in immunodeficient mice. Nat Protoc. 2007;2:247–50.PubMedCrossRef
15.
Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, Kotb M, Gillies SD, King M, Mangada J, et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174:6477–89.PubMedCrossRef
16.
Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, Ueyama Y, Koyanagi Y, Sugamura K, Tsuji K, et al. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100:3175–82.PubMedCrossRef
17.
Ishikawa F, Livingston AG, Wingard JR, Nishikawa S, Ogawa M. An assay for long-term engrafting human hematopoietic cells based on newborn NOD/SCID/beta2-microglobulin(null) mice. Exp Hematol. 2002;30:488–94.PubMedCrossRef
18.
Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K, Nakahata T. Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model. Blood. 2003;102:873–80.PubMedCrossRef
19.
Agliano A, Martin-Padura I, Mancuso P, Marighetti P, Rabascio C, Pruneri G, Shultz LD, Bertolini F. Human acute leukemia cells injected in NOD/LtSz-scid/IL-2Rgamma null mice generate a faster and more efficient disease compared to other NOD/scid-related strains. Int J Cancer. 2008;123:2222–7.PubMedCrossRef
20.
Covassin L, Jangalwe S, Jouvet N, Laning J, Burzenski L, Shultz LD, Brehm MA. Human immune system development and survival of non-obese diabetic (NOD)-scid IL2rgamma(null) (NSG) mice engrafted with human thymus and autologous haematopoietic stem cells. Clin Exp Immunol. 2013;174:372–88.PubMedPubMedCentralCrossRef
21.
Ye W, Jiang Z, Li GX, Xiao Y, Lin S, Lai Y, Wang S, Li B, Jia B, Li Y, et al. Quantitative evaluation of the immunodeficiency of a mouse strain by tumor engraftments. J Hematol Oncol. 2015;8:59.PubMedPubMedCentralCrossRef
22.
Xiao Y, Jiang Z, Li Y, Ye W, Jia B, Zhang M, Xu Y, Wu D, Lai L, Chen Y, et al. ANGPTL7 regulates the expansion and repopulation of human hematopoietic stem and progenitor cells. Haematologica. 2015;100:585–94.PubMedPubMedCentralCrossRef
23.
Jiang Z, Deng M, Wei X, Ye W, Xiao Y, Lin S, Wang S, Li B, Liu X, Zhang G, et al. Heterogeneity of CD34 and CD38 expression in acute B lymphoblastic leukemia cells is reversible and not hierarchically organized. J Hematol Oncol. 2016;9:94.PubMedPubMedCentralCrossRef
24.
Ye W, Jiang Z, Lu X, Ren X, Deng M, Lin S, Xiao Y, Lin S, Wang S, Li B, et al.: GZD824 suppresses the growth of human B cell precursor acute lymphoblastic leukemia cells by inhibiting the SRC kinase and PI3K/AKT pathways. Oncotarget. 2016.
25.
Jiang Z, Jiang X, Chen S, Lai Y, Wei X, Li B, Lin S, Wang S, Wu Q, Liang Q, et al. Anti-GPC3-CAR T cells suppress the growth of tumor cells in patient-derived xenografts of hepatocellular carcinoma. Front Immunol. 2016;7:690.PubMedCrossRef
26.
Pavia-Jimenez A, Tcheuyap VT, Brugarolas J. Establishing a human renal cell carcinoma tumorgraft platform for preclinical drug testing. Nat Protoc. 2014;9:1848–59.PubMedPubMedCentralCrossRef
27.
Gock M, Kuhn F, Mullins CS, Krohn M, Prall F, Klar E, Linnebacher M. Tumor take rate optimization for colorectal carcinoma patient-derived xenograft models. Biomed Res Int. 2016;2016:1715053.PubMedPubMedCentralCrossRef
28.
Alkema NG, Tomar T, Duiker EW, Jan Meersma G, Klip H, van der Zee AG, Wisman GB, de Jong S. Biobanking of patient and patient-derived xenograft ovarian tumour tissue: efficient preservation with low and high fetal calf serum based methods. Sci Rep. 2015;5:14495.PubMedPubMedCentralCrossRef
29.
Fu X, Guadagni F, Hoffman RM. A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens. Proc Natl Acad Sci U S A. 1992;89:5645–9.PubMedPubMedCentralCrossRef
30.
Papapetrou EP. Patient-derived induced pluripotent stem cells in cancer research and precision oncology. Nat Med. 2016;22:1392–401.PubMedCrossRef
31.
King MA, Covassin L, Brehm MA, Racki W, Pearson T, Leif J, Laning J, Fodor W, Foreman O, Burzenski L, et al. Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex. Clin Exp Immunol. 2009;157:104–18.PubMedPubMedCentralCrossRef
32.
Holzapfel BM, Wagner F, Thibaudeau L, Levesque JP, Hutmacher DW. Concise review: humanized models of tumor immunology in the 21st century: convergence of cancer research and tissue engineering. Stem Cells. 2015;33:1696–704.PubMedCrossRef
33.
34.
Byrne AT, Alferez DG, Amant F, Annibali D, Arribas J, Biankin AV, Bruna A, Budinska E, Caldas C, Chang DK, et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Cancer. 2017;17:254–68.
35.
Ebinger S, Ozdemir EZ, Ziegenhain C, Tiedt S, Castro Alves C, Grunert M, Dworzak M, Lutz C, Turati VA, Enver T, et al. Characterization of rare, dormant, and therapy-resistant cells in acute lymphoblastic leukemia. Cancer Cell. 2016;30:849–62.PubMedPubMedCentralCrossRef
36.
Klco JM, Spencer DH, Miller CA, Griffith M, Lamprecht TL, O’Laughlin M, Fronick C, Magrini V, Demeter RT, Fulton RS, et al. Functional heterogeneity of genetically defined subclones in acute myeloid leukemia. Cancer Cell. 2014;25:379–92.PubMedPubMedCentralCrossRef
37.
Kreso A, O’Brien CA, van Galen P, Gan OI, Notta F, Brown AM, Ng K, Ma J, Wienholds E, Dunant C, et al. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science. 2013;339:543–8.PubMedCrossRef
38.
Marusyk A, Tabassum DP, Altrock PM, Almendro V, Michor F, Polyak K. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature. 2014;514:54–8.PubMedPubMedCentralCrossRef
39.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.PubMedCrossRef
40.
Wang J, An H, Mayo MW, Baldwin AS, Yarbrough WG. LZAP, a putative tumor suppressor, selectively inhibits NF-kappaB. Cancer Cell. 2007;12:239–51.PubMedCrossRef
41.
Wang H, Vardy LA, Tan CP, Loo JM, Guo K, Li J, Lim SG, Zhou J, Chng WJ, Ng SB, et al. PCBP1 suppresses the translation of metastasis-associated PRL-3 phosphatase. Cancer Cell. 2010;18:52–62.PubMedCrossRef
42.
Domingo-Domenech J, Vidal SJ, Rodriguez-Bravo V, Castillo-Martin M, Quinn SA, Rodriguez-Barrueco R, Bonal DM, Charytonowicz E, Gladoun N, de la Iglesia-Vicente J, et al. Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells. Cancer Cell. 2012;22:373–88.PubMedCrossRef
43.
Yang L, Lin C, Jin C, Yang JC, Tanasa B, Li W, Merkurjev D, Ohgi KA, Meng D, Zhang J, et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature. 2013;500:598–602.PubMedPubMedCentralCrossRef
44.
Fox RG, Lytle NK, Jaquish DV, Park FD, Ito T, Bajaj J, Koechlein CS, Zimdahl B, Yano M, Kopp JL, et al. Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma. Nature. 2016;534:407–11.PubMedPubMedCentralCrossRef
45.
Lee JK, Phillips JW, Smith BA, Park JW, Stoyanova T, McCaffrey EF, Baertsch R, Sokolov A, Meyerowitz JG, Mathis C, et al. N-Myc drives neuroendocrine prostate cancer initiated from human prostate epithelial cells. Cancer Cell. 2016;29:536–47.PubMedPubMedCentralCrossRef
46.
Nucera S, Giustacchini A, Boccalatte F, Calabria A, Fanciullo C, Plati T, Ranghetti A, Garcia-Manteiga J, Cittaro D, Benedicenti F, et al. miRNA-126 orchestrates an oncogenic program in B cell precursor acute lymphoblastic leukemia. Cancer Cell. 2016;29:905–21.PubMedCrossRef
47.
Berger AH, Brooks AN, Wu X, Shrestha Y, Chouinard C, Piccioni F, Bagul M, Kamburov A, Imielinski M, Hogstrom L, et al. High-throughput phenotyping of lung cancer somatic mutations. Cancer Cell. 2016;30:214–28.PubMedCrossRef
48.
Pearson AT, Finkel KA, Warner KA, Nor F, Tice D, Martins MD, Jackson TL, Nor JE. Patient-derived xenograft (PDX) tumors increase growth rate with time. Oncotarget. 2016;7:7993–8005.PubMedPubMedCentral
49.
Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011;476:346–50.PubMedPubMedCentralCrossRef
50.
Lawson DA, Bhakta NR, Kessenbrock K, Prummel KD, Yu Y, Takai K, Zhou A, Eyob H, Balakrishnan S, Wang CY, et al. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature. 2015;526:131–5.PubMedPubMedCentralCrossRef
51.
Giuliano M, Herrera S, Christiny P, Shaw C, Creighton CJ, Mitchell T, Bhat R, Zhang X, Mao S, Dobrolecki LE, et al. Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis. Breast Cancer Res. 2015;17:3.PubMedPubMedCentralCrossRef
52.
Torphy RJ, Tignanelli CJ, Kamande JW, Moffitt RA, Herrera Loeza SG, Soper SA, Yeh JJ. Circulating tumor cells as a biomarker of response to treatment in patient-derived xenograft mouse models of pancreatic adenocarcinoma. PLoS One. 2014;9:e89474.PubMedPubMedCentralCrossRef
53.
Williams ES, Rodriguez-Bravo V, Chippada-Venkata U, De Ia Iglesia-Vicente J, Gong Y, Galsky M, Oh W, Cordon-Cardo C, Domingo-Domenech J: Generation of prostate cancer patient derived xenograft models from circulating tumor cells. J Vis Exp. 2015:53182.
54.
Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, et al. Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science. 2014;345:216–20.PubMedPubMedCentralCrossRef
55.
Pascual G, Avgustinova A, Mejetta S, Martin M, Castellanos A, Attolini CS, Berenguer A, Prats N, Toll A, Hueto JA, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature. 2017;541:41–5.PubMedCrossRef
56.
Powell E, Shao J, Yuan Y, Chen HC, Cai S, Echeverria GV, Mistry N, Decker KF, Schlosberg C, Do KA, et al. p53 deficiency linked to B cell translocation gene 2 (BTG2) loss enhances metastatic potential by promoting tumor growth in primary and metastatic sites in patient-derived xenograft (PDX) models of triple-negative breast cancer. Breast Cancer Res. 2016;18:13.PubMedPubMedCentralCrossRef
57.
Dobbin ZC, Katre AA, Steg AD, Erickson BK, Shah MM, Alvarez RD, Conner MG, Schneider D, Chen D, Landen CN. Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer. Oncotarget. 2014;5:8750–64.PubMedPubMedCentralCrossRef
58.
Lohse I, Borgida A, Cao P, Cheung M, Pintilie M, Bianco T, Holter S, Ibrahimov E, Kumareswaran R, Bristow RG, et al. BRCA1 and BRCA2 mutations sensitize to chemotherapy in patient-derived pancreatic cancer xenografts. Br J Cancer. 2015;113:425–32.PubMedPubMedCentralCrossRef
59.
Mizrachi A, Shamay Y, Shah J, Brook S, Soong J, Rajasekhar VK, Humm JL, Healey JH, Powell SN, Baselga J, et al. Tumour-specific PI3K inhibition via nanoparticle-targeted delivery in head and neck squamous cell carcinoma. Nat Commun. 2017;8:14292.PubMedPubMedCentralCrossRef
60.
Bago JR, Alfonso-Pecchio A, Okolie O, Dumitru R, Rinkenbaugh A, Baldwin AS, Miller CR, Magness ST, Hingtgen SD. Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma. Nat Commun. 2016;7:10593.PubMedPubMedCentralCrossRef
61.
Yano S, Hiroshima Y, Maawy A, Kishimoto H, Suetsugu A, Miwa S, Toneri M, Yamamoto M, Katz MH, Fleming JB, et al. Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery. Cancer Gene Ther. 2015;22:344–50.PubMedPubMedCentralCrossRef
62.
Hiroshima Y, Maawy A, Metildi CA, Zhang Y, Uehara F, Miwa S, Yano S, Sato S, Murakami T, Momiyama M, et al. Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system. J Laparoendosc Adv Surg Tech A. 2014;24:241–7.PubMedPubMedCentralCrossRef
63.
Willey CD, Gilbert AN, Anderson JC, Gillespie GY. Patient-derived xenografts as a model system for radiation research. Semin Radiat Oncol. 2015;25:273–80.PubMedPubMedCentralCrossRef
64.
Motomura T, Ueda K, Ohtani S, Hansen E, Ji L, Ito K, Saito K, Sugita Y, Nose Y. Evaluation of systemic external microwave hyperthermia for treatment of pleural metastasis in orthotopic lung cancer model. Oncol Rep. 2010;24:591–8.PubMedCrossRef
65.
Rubio-Viqueira B, Jimeno A, Cusatis G, Zhang X, Iacobuzio-Donahue C, Karikari C, Shi C, Danenberg K, Danenberg PV, Kuramochi H, et al. An in vivo platform for translational drug development in pancreatic cancer. Clin Cancer Res. 2006;12:4652–61.PubMedCrossRef
66.
Zhang XC, Zhang J, Li M, Huang XS, Yang XN, Zhong WZ, Xie L, Zhang L, Zhou M, Gavine P, et al. 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. J Transl Med. 2013;11:168.PubMedPubMedCentralCrossRef
67.
Merk J, Rolff J, Becker M, Leschber G, Fichtner I. Patient-derived xenografts of non-small-cell lung cancer: a pre-clinical model to evaluate adjuvant chemotherapy? Eur J Cardiothorac Surg. 2009;36:454–9.PubMedCrossRef
68.
Fiebig HH, Schuler J, Bausch N, Hofmann M, Metz T, Korrat A. Gene signatures developed from patient tumor explants grown in nude mice to predict tumor response to 11 cytotoxic drugs. Cancer Genomics Proteomics. 2007;4:197–209.PubMed
69.
Marangoni E, Vincent-Salomon A, Auger N, Degeorges A, Assayag F, de Cremoux P, de Plater L, Guyader C, De Pinieux G, Judde JG, et al. A new model of patient tumor-derived breast cancer xenografts for preclinical assays. Clin Cancer Res. 2007;13:3989–98.PubMedCrossRef
70.
de Plater L, Lauge A, Guyader C, Poupon MF, Assayag F, de Cremoux P, Vincent-Salomon A, Stoppa-Lyonnet D, Sigal-Zafrani B, Fontaine JJ, et al. Establishment and characterisation of a new breast cancer xenograft obtained from a woman carrying a germline BRCA2 mutation. Br J Cancer. 2010;103:1192–200.PubMedPubMedCentralCrossRef
71.
Jin K, Li G, Cui B, Zhang J, Lan H, Han N, Xie B, Cao F, He K, Wang H, et al. Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases. PLoS One. 2011;6:e28384.PubMedPubMedCentralCrossRef
72.
Yoshida T, Kinoshita H, Segawa T, Nakamura E, Inoue T, Shimizu Y, Kamoto T, Ogawa O. Antiandrogen bicalutamide promotes tumor growth in a novel androgen-dependent prostate cancer xenograft model derived from a bicalutamide-treated patient. Cancer Res. 2005;65:9611–6.PubMedCrossRef
73.
Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, Arcaroli JJ, Messersmith WA, Eckhardt SG. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol. 2012;9:338–50.PubMedPubMedCentralCrossRef
74.
Bousquet G, Janin A. Patient-derived xenograft: an adjuvant technology for the treatment of metastatic disease. Pathobiology. 2016;83:170–6.PubMedCrossRef
75.
Ter Brugge P, Kristel P, van der Burg E, Boon U, de Maaker M, Lips E, Mulder L, de Ruiter J, Moutinho C, Gevensleben H, et al. Mechanisms of therapy resistance in patient-derived xenograft models of BRCA1-deficient breast cancer. J Natl Cancer Inst 2016, 108.
76.
Krumbach R, Schuler J, Hofmann M, Giesemann T, Fiebig HH, Beckers T. Primary resistance to cetuximab in a panel of patient-derived tumour xenograft models: activation of MET as one mechanism for drug resistance. Eur J Cancer. 2011;47:1231–43.PubMedCrossRef
77.
Bradford JR, Wappett M, Beran G, Logie A, Delpuech O, Brown H, Boros J, Camp NJ, McEwen R, Mazzola AM, et al. Whole transcriptome profiling of patient-derived xenograft models as a tool to identify both tumor and stromal specific biomarkers. Oncotarget. 2016;7:20773–87.PubMedPubMedCentral
78.
Metildi CA, Kaushal S, Luiken GA, Talamini MA, Hoffman RM, Bouvet M. Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model. J Surg Oncol. 2014;109:451–8.PubMedCrossRef
79.
Zhao Q, Zhou H, Liu Q, Cao Y, Wang G, Hu A, Ruan L, Wang S, Bo Q, Chen W, et al. Prognostic value of the expression of cancer stem cell-related markers CD133 and CD44 in hepatocellular carcinoma: from patients to patient-derived tumor xenograft models. Oncotarget. 2016;7:47431–43.PubMedPubMedCentral
80.
Skowron KB, Pitroda SP, Namm JP, Balogun O, Beckett MA, Zenner ML, Fayanju O, Huang X, Fernandez C, Zheng W, et al. Basal tumor cell isolation and patient-derived xenograft engraftment identify high-risk clinical bladder cancers. Sci Rep. 2016;6:35854.PubMedPubMedCentralCrossRef
81.
Gardner EE, Lok BH, Schneeberger VE, Desmeules P, Miles LA, Arnold PK, Ni A, Khodos I, de Stanchina E, Nguyen T, et al. Chemosensitive relapse in small cell lung cancer proceeds through an EZH2-SLFN11 axis. Cancer Cell. 2017;31:286–99.PubMedCrossRef
82.
Zhou W, Yang Y, Xia J, Wang H, Salama ME, Xiong W, Xu H, Shetty S, Chen T, Zeng Z, et al. NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers. Cancer Cell. 2013;23:48–62.PubMedPubMedCentralCrossRef
83.
Leucci E, Vendramin R, Spinazzi M, Laurette P, Fiers M, Wouters J, Radaelli E, Eyckerman S, Leonelli C, Vanderheyden K, et al. Melanoma addiction to the long non-coding RNA SAMMSON. Nature. 2016;531:518–22.PubMedCrossRef
84.
Mitsiades CS, Mitsiades NS, McMullan CJ, Poulaki V, Shringarpure R, Akiyama M, Hideshima T, Chauhan D, Joseph M, Libermann TA, et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell. 2004;5:221–30.PubMedCrossRef
85.
Wang Y, Ding X, Wang S, Moser CD, Shaleh HM, Mohamed EA, Chaiteerakij R, Allotey LK, Chen G, Miyabe K, et al. Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein. Cancer Lett. 2016;380:163–73.PubMedCrossRef
86.
Siu IM, Ruzevick J, Zhao Q, Connis N, Jiao Y, Bettegowda C, Xia X, Burger PC, Hann CL, Gallia GL. Erlotinib inhibits growth of a patient-derived chordoma xenograft. PLoS One. 2013;8:e78895.PubMedPubMedCentralCrossRef
87.
Martin P, Stewart E, Pham NA, Mascaux C, Panchal D, Li M, Kim L, Sakashita S, Wang D, Sykes J, et al. Cetuximab inhibits T790M-mediated resistance to epidermal growth factor receptor tyrosine kinase inhibitor in a lung adenocarcinoma patient-derived xenograft mouse model. Clin Lung Cancer. 2016;17:375–83. e372.PubMedCrossRef
88.
Li J, Davies BR, Han S, Zhou M, Bai Y, Zhang J, Xu Y, Tang L, Wang H, Liu YJ, et al. The AKT inhibitor AZD5363 is selectively active in PI3KCA mutant gastric cancer, and sensitizes a patient-derived gastric cancer xenograft model with PTEN loss to Taxotere. J Transl Med. 2013;11:241.PubMedPubMedCentralCrossRef
89.
Jin K, Lan H, Cao F, Xu Z, Han N, Li G, He K, Teng L. Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism. Oncol Lett. 2012;3:1052–8.PubMedPubMedCentral
90.
Passaro D, Irigoyen M, Catherinet C, Gachet S, Da Costa De Jesus C, Lasgi C, Tran Quang C, Ghysdael J. CXCR4 is required for leukemia-initiating cell activity in T cell acute lymphoblastic leukemia. Cancer Cell. 2015;27:769–79.PubMedCrossRef
91.
Pitt LA, Tikhonova AN, Hu H, Trimarchi T, King B, Gong Y, Sanchez-Martin M, Tsirigos A, Littman DR, Ferrando AA, et al. CXCL12-producing vascular endothelial niches control acute T cell leukemia maintenance. Cancer Cell. 2015;27:755–68.PubMedPubMedCentralCrossRef
92.
Hai J, Sakashita S, Allo G, Ludkovski O, Ng C, Shepherd FA, Tsao MS. Inhibiting MDM2-p53 interaction suppresses tumor growth in patient-derived non-small cell lung cancer xenograft models. J Thorac Oncol. 2015;10:1172–80.PubMedCrossRef
93.
Gad H, Koolmeister T, Jemth AS, Eshtad S, Jacques SA, Strom CE, Svensson LM, Schultz N, Lundback T, Einarsdottir BO, et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature. 2014;508:215–21.PubMedCrossRef
94.
Esber N, Cherbonnier C, Resche-Rigon M, Hamze A, Alami M, Fagart J, Loosfelt H, Lombes M, Chabbert-Buffet N. Anti-tumoral effects of anti-progestins in a patient-derived breast cancer xenograft model. Horm Cancer. 2016;7:137–47.PubMedCrossRef
95.
Lu J, Li G, He K, Jiang W, Xu C, Li Z, Wang H, Wang W, Wang H, Teng X, Teng L. Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer. J Transl Med. 2015;13:42.PubMedPubMedCentralCrossRef
96.
Peraldo Neia C, Cavalloni G, Chiorino G, Ostano P, Aglietta M, Leone F: Gene and microRNA modulation upon trabectedin treatment in a human intrahepatic cholangiocarcinoma paired patient derived xenograft and cell line. Oncotarget 2016.
97.
Zou HY, Friboulet L, Kodack DP, Engstrom LD, Li Q, West M, Tang RW, Wang H, Tsaparikos K, Wang J, et al. PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell. 2015;28:70–81.PubMedPubMedCentralCrossRef
98.
Wang CJ, Tong PJ, Zhu MY. The combinational therapy of trastuzumab and cetuximab inhibits tumor growth in a patient-derived tumor xenograft model of gastric cancer. Clin Transl Oncol. 2016;18:507–14.PubMedCrossRef
99.
Wu X, Zhang J, Zhen R, Lv J, Zheng L, Su X, Zhu G, Gavine PR, Xu S, Lu S, et al. Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models. J Transl Med. 2012;10:180.PubMedPubMedCentralCrossRef
100.
Zhao X, Subramanian S. Intrinsic resistance of solid tumors to immune checkpoint blockade therapy. Cancer Res. 2017;77:817–22.PubMedCrossRef
101.
Kurtova AV, Xiao J, Mo Q, Pazhanisamy S, Krasnow R, Lerner SP, Chen F, Roh TT, Lay E, Ho PL, Chan KS. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance. Nature. 2015;517:209–13.PubMedCrossRef
102.
Murakami T, Igarashi K, Kawaguchi K, Kiyuna T, Zhang Y, Zhao M, Hiroshima Y, Nelson SD, Dry SM, Li Y, et al. Tumor-targeting Salmonella typhimurium A1-R regresses an osteosarcoma in a patient-derived xenograft model resistant to a molecular-targeting drug. Oncotarget. 2017;8:8035–42.PubMed
103.
Murakami T, DeLong J, Eilber FC, Zhao M, Zhang Y, Zhang N, Singh A, Russell T, Deng S, Reynoso J, et al. Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model. Oncotarget. 2016;7:12783–90.PubMedPubMedCentral
104.
Yamamoto M, Zhao M, Hiroshima Y, Zhang Y, Shurell E, Eilber FC, Bouvet M, Noda M, Hoffman RM. Efficacy of tumor-targeting Salmonella A1-R on a melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse model. PLoS One. 2016;11:e0160882.PubMedPubMedCentralCrossRef
105.
Stojdl DF, Lichty BD, TenOever BR, Paterson JM, Power AT, Knowles S, Marius R, Reynard J, Poliquin L, Atkins H, et al. VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell. 2003;4:263–75.PubMedCrossRef
106.
Berghauser Pont LM, Kleijn A, Kloezeman JJ, van den Bossche W, Kaufmann JK, de Vrij J, Leenstra S, Dirven CM, Lamfers ML. The HDAC inhibitors Scriptaid and LBH589 combined with the oncolytic virus Delta24-RGD exert enhanced anti-tumor efficacy in patient-derived glioblastoma cells. PLoS One. 2015;10:e0127058.PubMedPubMedCentralCrossRef
107.
Allen C, Opyrchal M, Aderca I, Schroeder MA, Sarkaria JN, Domingo E, Federspiel MJ, Galanis E. Oncolytic measles virus strains have significant antitumor activity against glioma stem cells. Gene Ther. 2013;20:444–9.PubMedCrossRef
108.
Deng M, Jiang Z, Li Y, Zhou Y, Li J, Wang X, Yao Y, Wang W, Li P, Xu B. Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models. Oncotarget. 2016;7:82200–12.PubMedPubMedCentral
109.
Wei W, Shin YS, Xue M, Matsutani T, Masui K, Yang H, Ikegami S, Gu Y, Herrmann K, Johnson D, et al. Single-cell phosphoproteomics resolves adaptive signaling dynamics and informs targeted combination therapy in glioblastoma. Cancer Cell. 2016;29:563–73.PubMedPubMedCentralCrossRef
110.
Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, et al. Overcoming therapeutic resistance in HER2-positive breast cancers with CDK4/6 inhibitors. Cancer Cell. 2016;29:255–69.PubMedPubMedCentralCrossRef
111.
Ham J, Costa C, Sano R, Lochmann TL, Sennott EM, Patel NU, Dastur A, Gomez-Caraballo M, Krytska K, Hata AN, et al. Exploitation of the apoptosis-primed state of MYCN-amplified neuroblastoma to develop a potent and specific targeted therapy combination. Cancer Cell. 2016;29:159–72.PubMedPubMedCentralCrossRef
112.
Vora SR, Juric D, Kim N, Mino-Kenudson M, Huynh T, Costa C, Lockerman EL, Pollack SF, Liu M, Li X, et al. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors. Cancer Cell. 2014;26:136–49.PubMedPubMedCentralCrossRef
113.
Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A, Bernards R. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483:100–3.PubMedCrossRef
114.
Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, Jan M, Cha AC, Chan CK, Tan BT, et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell. 2010;142:699–713.PubMedPubMedCentralCrossRef
115.
Johnson JI, Decker S, Zaharevitz D, Rubinstein LV, Venditti J, Schepartz S, Kalyandrug S, Christian M, Arbuck S, Hollingshead M, Sausville EA. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer. 2001;84:1424–31.PubMedPubMedCentralCrossRef
116.
Sugimoto K, Hayakawa F, Shimada S, Morishita T, Shimada K, Katakai T, Tomita A, Kiyoi H, Naoe T. Discovery of a drug targeting microenvironmental support for lymphoma cells by screening using patient-derived xenograft cells. Sci Rep. 2015;5:13054.PubMedPubMedCentralCrossRef
117.
Bruna A, Rueda OM, Greenwood W, Batra AS, Callari M, Batra RN, Pogrebniak K, Sandoval J, Cassidy JW, Tufegdzic-Vidakovic A, et al. A Biobank of breast cancer explants with preserved intra-tumor heterogeneity to screen anticancer compounds. Cell. 2016;167:260–74. e222.PubMedPubMedCentralCrossRef
118.
Townsend EC, Murakami MA, Christodoulou A, Christie AL, Koster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, et al. The public repository of xenografts enables discovery and randomized phase II-like trials in mice. Cancer Cell. 2016;29:574–86.PubMedPubMedCentralCrossRef
119.
Welsch ME, Kaplan A, Chambers JM, Stokes ME, Bos PH, Zask A, Zhang Y, Sanchez-Martin M, Badgley MA, Huang CS, et al. Multivalent small-molecule pan-RAS inhibitors. Cell. 2017;168:878–89. e829.PubMedCrossRef
120.
Procko E, Berguig GY, Shen BW, Song Y, Frayo S, Convertine AJ, Margineantu D, Booth G, Correia BE, Cheng Y, et al. A computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein induces apoptosis in infected cells. Cell. 2014;157:1644–56.PubMedPubMedCentralCrossRef
121.
Posey Jr AD, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, Stone JD, Madsen TD, Schreiber K, Haines KM, et al. Engineered CAR T cells targeting the cancer-associated Tn-glycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity. 2016;44:1444–54.PubMedPubMedCentralCrossRef
122.
Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M, Ingaramo M, Smith JP, Walker AJ, Kohler ME, Venkateshwara VR, et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med. 2015;21:581–90.PubMedPubMedCentralCrossRef
123.
Adusumilli PS, Cherkassky L, Villena-Vargas J, Colovos C, Servais E, Plotkin J, Jones DR, Sadelain M. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014;6:261–151.CrossRef
124.
Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJ, Hamieh M, Cunanan KM, Odak A, Gonen M, Sadelain M. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017;543:113–7.PubMedCrossRef
125.
Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science. 2015;350:aab4077.PubMedPubMedCentralCrossRef
126.
Boice M, Salloum D, Mourcin F, Sanghvi V, Amin R, Oricchio E, Jiang M, Mottok A, Denis-Lagache N, Ciriello G, et al. Loss of the HVEM tumor suppressor in lymphoma and restoration by modified CAR-T cells. Cell. 2016;167:405–18. e413.PubMedCrossRef
127.
Morton JJ, Bird G, Keysar SB, Astling DP, Lyons TR, Anderson RT, Glogowska MJ, Estes P, Eagles JR, Le PN, et al. XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer. Oncogene. 2016;35:290–300.PubMedCrossRef
128.
Eirew P, Steif A, Khattra J, Ha G, Yap D, Farahani H, Gelmon K, Chia S, Mar C, Wan A, et al. Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution. Nature. 2015;518:422–6.PubMedCrossRef
129.
Gros A, Parkhurst MR, Tran E, Pasetto A, Robbins PF, Ilyas S, Prickett TD, Gartner JJ, Crystal JS, Roberts IM, et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med. 2016;22:433–8.PubMedCrossRef
130.
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.PubMedCrossRef
131.
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.PubMedPubMedCentralCrossRef
132.
Pratesi G, Petrangolini G, Tortoreto M, Addis A, Belluco S, Rossini A, Selleri S, Rumio C, Menard S, Balsari A. Therapeutic synergism of gemcitabine and CpG-oligodeoxynucleotides in an orthotopic human pancreatic carcinoma xenograft. Cancer Res. 2005;65:6388–93.PubMedCrossRef
133.
Long D, Liu T, Tan L, Shi H, Liang P, Tang S, Wu Q, Yu J, Dou J, Meng X. Multisynergistic platform for tumor therapy by mild microwave irradiation-activated chemotherapy and enhanced ablation. ACS Nano. 2016.
134.
Herrero A, Pinto A, Colon-Bolea P, Casar B, Jones M, Agudo-Ibanez L, Vidal R, Tenbaum SP, Nuciforo P, Valdizan EM, et al. Small molecule inhibition of ERK dimerization prevents tumorigenesis by RAS-ERK pathway oncogenes. Cancer Cell. 2015;28:170–82.PubMedCrossRef
135.
Lee EM, Yee D, Busfield SJ, McManus JF, Cummings N, Vairo G, Wei A, Ramshaw HS, Powell JA, Lopez AF, et al. Efficacy of an Fc-modified anti-CD123 antibody (CSL362) combined with chemotherapy in xenograft models of acute myelogenous leukemia in immunodeficient mice. Haematologica. 2015;100:914–26.PubMedPubMedCentralCrossRef
136.
Jin K, Lan H, Cao F, Han N, Xu Z, Li G, He K, Teng L. Differential response to EGFR- and VEGF-targeted therapies in patient-derived tumor tissue xenograft models of colon carcinoma and related metastases. Int J Oncol. 2012;41:583–8.PubMed
137.
Sykes DB, Kfoury YS, Mercier FE, Wawer MJ, Law JM, Haynes MK, Lewis TA, Schajnovitz A, Jain E, Lee D, et al. Inhibition of dihydroorotate dehydrogenase overcomes differentiation blockade in acute myeloid leukemia. Cell. 2016;167:171–86. e115.PubMedCrossRef
138.
Mohammad HP, Smitheman KN, Kamat CD, Soong D, Federowicz KE, Van Aller GS, Schneck JL, Carson JD, Liu Y, Butticello M, et al. A DNA hypomethylation signature predicts antitumor activity of LSD1 inhibitors in SCLC. Cancer Cell. 2015;28:57–69.PubMedCrossRef
139.
Wu SC, Li LS, Kopp N, Montero J, Chapuy B, Yoda A, Christie AL, Liu H, Christodoulou A, van Bodegom D, et al. Activity of the type II JAK2 inhibitor CHZ868 in B cell acute lymphoblastic leukemia. Cancer Cell. 2015;28:29–41.PubMedPubMedCentralCrossRef
140.
Cerezo M, Lehraiki A, Millet A, Rouaud F, Plaisant M, Jaune E, Botton T, Ronco C, Abbe P, Amdouni H, et al. Compounds triggering ER stress exert anti-melanoma effects and overcome BRAF inhibitor resistance. Cancer Cell. 2016;29:805–19.PubMedCrossRef
141.
Veschi V, Liu Z, Voss TC, Ozbun L, Gryder B, Yan C, Hu Y, Ma A, Jin J, Mazur SJ, et al. Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017;31:50–63.PubMedCrossRef
142.
Huang X, Motea EA, Moore ZR, Yao J, Dong Y, Chakrabarti G, Kilgore JA, Silvers MA, Patidar PL, Cholka A, et al. Leveraging an NQO1 bioactivatable drug for tumor-selective use of poly(ADP-ribose) polymerase inhibitors. Cancer Cell. 2016;30:940–52.PubMedCrossRef
143.
Wang L, Yu Y, Chow DC, Yan F, Hsu CC, Stossi F, Mancini MA, Palzkill T, Liao L, Zhou S, et al. Characterization of a steroid receptor coactivator small molecule stimulator that overstimulates cancer cells and leads to cell stress and death. Cancer Cell. 2015;28:240–52.PubMedPubMedCentralCrossRef
144.
Chauhan D, Tian Z, Nicholson B, Kumar KG, Zhou B, Carrasco R, McDermott JL, Leach CA, Fulcinniti M, Kodrasov MP, et al. A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell. 2012;22:345–58.PubMedPubMedCentralCrossRef
145.
Chen W, Hill H, Christie A, Kim MS, Holloman E, Pavia-Jimenez A, Homayoun F, Ma Y, Patel N, Yell P, et al. Targeting renal cell carcinoma with a HIF-2 antagonist. Nature. 2016;539:112–7.PubMedPubMedCentralCrossRef
146.
Bono F, De Smet F, Herbert C, De Bock K, Georgiadou M, Fons P, Tjwa M, Alcouffe C, Ny A, Bianciotto M, et al. Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties. Cancer Cell. 2013;23:477–88.PubMedCrossRef
147.
Sakamoto H, Tsukaguchi T, Hiroshima S, Kodama T, Kobayashi T, Fukami TA, Oikawa N, Tsukuda T, Ishii N, Aoki Y. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011;19:679–90.PubMedCrossRef
148.
Gumireddy K, Reddy MV, Cosenza SC, Boominathan R, Baker SJ, Papathi N, Jiang J, Holland J, Reddy EP. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell. 2005;7:275–86.PubMedCrossRef
149.
Plescia J, Salz W, Xia F, Pennati M, Zaffaroni N, Daidone MG, Meli M, Dohi T, Fortugno P, Nefedova Y, et al. Rational design of shepherdin, a novel anticancer agent. Cancer Cell. 2005;7:457–68.PubMedCrossRef
150.
Solit DB, Garraway LA, Pratilas CA, Sawai A, Getz G, Basso A, Ye Q, Lobo JM, She Y, Osman I, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature. 2006;439:358–62.PubMedCrossRef
151.
Visentin B, Vekich JA, Sibbald BJ, Cavalli AL, Moreno KM, Matteo RG, Garland WA, Lu Y, Yu S, Hall HS, et al. Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell. 2006;9:225–38.PubMedCrossRef
152.
Thomas EK, Cancelas JA, Chae HD, Cox AD, Keller PJ, Perrotti D, Neviani P, Druker BJ, Setchell KD, Zheng Y, et al. Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. Cancer Cell. 2007;12:467–78.PubMedCrossRef
153.
Nickeleit I, Zender S, Sasse F, Geffers R, Brandes G, Sorensen I, Steinmetz H, Kubicka S, Carlomagno T, Menche D, et al. Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition. Cancer Cell. 2008;14:23–35.PubMedCrossRef
154.
Hahn CK, Berchuck JE, Ross KN, Kakoza RM, Clauser K, Schinzel AC, Ross L, Galinsky I, Davis TN, Silver SJ, et al. Proteomic and genetic approaches identify Syk as an AML target. Cancer Cell. 2009;16:281–94.PubMedPubMedCentralCrossRef
155.
Schimmer AD, Welsh K, Pinilla C, Wang Z, Krajewska M, Bonneau MJ, Pedersen IM, Kitada S, Scott FL, Bailly-Maitre B, et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell. 2004;5:25–35.PubMedCrossRef
156.
Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324:787–90.PubMedPubMedCentralCrossRef
157.
Andersen RJ, Mawji NR, Wang J, Wang G, Haile S, Myung JK, Watt K, Tam T, Yang YC, Banuelos CA, et al. Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor. Cancer Cell. 2010;17:535–46.PubMedCrossRef
158.
Raj L, Ide T, Gurkar AU, Foley M, Schenone M, Li X, Tolliday NJ, Golub TR, Carr SA, Shamji AF, et al. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature. 2011;475:231–4.PubMedPubMedCentralCrossRef
159.
Mason JM, Lin DC, Wei X, Che Y, Yao Y, Kiarash R, Cescon DW, Fletcher GC, Awrey DE, Bray MR, et al. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell. 2014;26:163–76.PubMedCrossRef
160.
Han B, Park D, Li R, Xie M, Owonikoko TK, Zhang G, Sica GL, Ding C, Zhou J, Magis AT, et al. Small-molecule Bcl2 BH4 antagonist for lung cancer therapy. Cancer Cell. 2015;27:852–63.PubMedPubMedCentralCrossRef
161.
Girotti MR, Lopes F, Preece N, Niculescu-Duvaz D, Zambon A, Davies L, Whittaker S, Saturno G, Viros A, Pedersen M, et al. Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer Cell. 2015;27:85–96.PubMedPubMedCentralCrossRef
162.
Flaveny CA, Griffett K, El-Gendy Bel D, Kazantzis M, Sengupta M, Amelio AL, Chatterjee A, Walker J, Solt LA, Kamenecka TM, Burris TP. Broad anti-tumor activity of a small molecule that selectively targets the Warburg effect and lipogenesis. Cancer Cell. 2015;28:42–56.PubMedPubMedCentralCrossRef
163.
Chen YN, LaMarche MJ, Chan HM, Fekkes P, Garcia-Fortanet J, Acker MG, Antonakos B, Chen CH, Chen Z, Cooke VG, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016;535:148–52.PubMedCrossRef
164.
Storm EE, Durinck S, de Sousa e Melo F, Tremayne J, Kljavin N, Tan C, Ye X, Chiu C, Pham T, Hongo JA, et al. Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature. 2016;529:97–100.PubMedCrossRef
165.
Anderson DJ, Le Moigne R, Djakovic S, Kumar B, Rice J, Wong S, Wang J, Yao B, Valle E, Kiss von Soly S, et al. Targeting the AAA ATPase p97 as an approach to treat cancer through disruption of protein homeostasis. Cancer Cell. 2015;28:653–65.PubMedPubMedCentralCrossRef
166.
Veitonmaki N, Hansson M, Zhan F, Sundberg A, Lofstedt T, Ljungars A, Li ZC, Martinsson-Niskanen T, Zeng M, Yang Y, et al. A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer Cell. 2013;23:502–15.PubMedCrossRef
167.
Milhollen MA, Thomas MP, Narayanan U, Traore T, Riceberg J, Amidon BS, Bence NF, Bolen JB, Brownell J, Dick LR, et al. Treatment-emergent mutations in NAEbeta confer resistance to the NEDD8-activating enzyme inhibitor MLN4924. Cancer Cell. 2012;21:388–401.PubMedCrossRef
168.
Etchin J, Montero J, Berezovskaya A, Le BT, Kentsis A, Christie AL, Conway AS, Chen WC, Reed C, Mansour MR, et al. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice. Leukemia. 2016;30:190–9.PubMedCrossRef
169.
Alves F, Borchers U, Padge B, Augustin H, Nebendahl K, Kloppel G, Tietze LF. Inhibitory effect of a matrix metalloproteinase inhibitor on growth and spread of human pancreatic ductal adenocarcinoma evaluated in an orthotopic severe combined immunodeficient (SCID) mouse model. Cancer Lett. 2001;165:161–70.PubMedCrossRef
Metadata
Title
Current status and perspectives of patient-derived xenograft models in cancer research
Authors
Yunxin Lai
Xinru Wei
Shouheng Lin
Le Qin
Lin Cheng
Peng Li
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0470-7

Other articles of this Issue 1/2017

Journal of Hematology & Oncology 1/2017 Go to the issue

Research

Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein

Research

Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study

Review

Emerging therapies for breast cancer

Letter to the Editor

T cells bearing anti-CD19 and/or anti-CD38 chimeric antigen receptors effectively abrogate primary double-hit lymphoma cells

Rapid communication

Activity of trabectedin and the PARP inhibitor rucaparib in soft-tissue sarcomas

Review

Blocking the PD-1/PD-L1 pathway in glioma: a potential new treatment strategy
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits