High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response

Nature Medicine

Volumn 21, Issue 11, 2015, Pages 1318-1325

  Gao, Hui ^a   Korn, Joshua M ^a   Ferretti, Stéphane ^b   Monahan, John E ^a   Wang, Youzhen ^c   Singh, Mallika ^d,e   Zhang, Chao ^c,f   Schnell, Christian ^b   Yang, Guizhi ^a   Zhang, Yun ^c   Balbin, O Alejandro ^a   Barbe, Stéphanie ^b   Cai, Hongbo ^a   Casey, Fergal ^d   Chatterjee, Susmita ^d   Chiang, Derek Y ^a   Chuai, Shannon ^c   Cogan, Shawn M ^a   Collins, Scott D ^a   Dammassa, Ernesta ^b   Ebel, Nicolas ^b   Embry, Millicent ^d   Green, John ^a   Kauffmann, Audrey ^b   Kowal, Colleen ^a   Leary, Rebecca J ^a   Lehar, Joseph ^a   Liang, Ying ^c   Loo, Alice ^a   Lorenzana, Edward ^d   Robert McDonald, E ^a   McLaughlin, Margaret E ^a   Merkin, Jason ^a   Meyer, Ronald ^a   Naylor, Tara L ^a   Patawaran, Montesa ^d   Reddy, Anupama ^a,e   Röelli, Claudia ^b   Ruddy, David A ^a   Salangsang, Fernando ^d   Santacroce, Francesca ^b   Singh, Angad P ^a   Tang, Yan ^d   Tinetto, Walter ^b   Tobler, Sonja ^b   Velazquez, Roberto ^a   Venkatesan, Kavitha ^a   Von Arx, Fabian ^b   Wang, Hui Qin ^a,h   Wang, Zongyao ^c   Wiesmann, Marion ^b   Wyss, Daniel ^b   Xu, Fiona ^c   Bitter, Hans ^a   Atadja, Peter ^c   Lees, Emma ^d   Hofmann, Francesco ^b   Li, En ^c   Keen, Nicholas ^a   Cozens, Robert ^b   Jensen, Michael Rugaard ^b   Pryer, Nancy K ^d,g   Williams, Juliet A ^a   Sellers, William R ^a   more..

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

^c Novartis Institutes for Biomedical Research   (China)

^d Novartis Institutes for Biomedical Research   (United States)

^e Patronus Therapeutics   (United States)

^f Schneider Electric IT Business   (China)

^g BIOMARIN PHARMACEUTICAL INC   (United States)

^h DUKE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPELISIB; ANTINEOPLASTIC AGENT; B RAF KINASE; BINIMETINIB; BUPARLISIB; CERITINIB; CGM 097; CLR 457; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE INHIBITOR 2A; ENCORAFENIB; ERLOTINIB; FIGITUMUMAB; HEPATOCYTE NUCLEAR FACTOR 1; INFIGRATINIB; LGH 47; LGW 813; LJM 716; MITOGEN ACTIVATED PROTEIN KINASE; N [1 CYCLOHEXYL 2 [2 [4 (4 FLUOROBENZOYL) 2 THIAZOLYL] 1 PYRROLIDINYL] 2 OXOETHYL] 2 (METHYLAMINO)PROPANAMIDE; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN MDM2; PROTEIN MDMX; RETINOBLASTOMA BINDING PROTEIN 2; RIBOCICLIB; TAS 266; TRAMETINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; WNT 974;

ADULT; ARTICLE; BREAST CARCINOMA; CANCER CELL CULTURE; COLORECTAL CANCER; CUTANEOUS MELANOMA; DRUG RESPONSE; ESOPHAGUS CANCER; FEMALE; GAIN OF FUNCTION MUTATION; GENETIC ASSOCIATION; GENOTYPE; HIGH THROUGHPUT SCREENING; HUMAN; KIDNEY CARCINOMA; MELANOMA; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARY CARCINOMA; PANCREAS ADENOCARCINOMA; PATIENT SELECTION; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; SOFT TISSUE SARCOMA; SOMATIC MUTATION; TUMOR XENOGRAFT; ANIMAL; BREAST NEOPLASMS; CANCER TRANSPLANTATION; CARCINOMA; CARCINOMA, NON-SMALL-CELL LUNG; CARCINOMA, PANCREATIC DUCTAL; COLORECTAL NEOPLASMS; DISEASE MODEL; DRUG SCREENING; LUNG NEOPLASMS; MOUSE; NEOPLASMS; PANCREATIC NEOPLASMS; PROCEDURES; REPRODUCIBILITY; SKIN NEOPLASMS; STOMACH NEOPLASMS;

ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CARCINOMA; CARCINOMA, NON-SMALL-CELL LUNG; CARCINOMA, PANCREATIC DUCTAL; COLORECTAL NEOPLASMS; DISEASE MODELS, ANIMAL; FEMALE; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; LUNG NEOPLASMS; MELANOMA; MICE; NEOPLASM TRANSPLANTATION; NEOPLASMS; PANCREATIC NEOPLASMS; REPRODUCIBILITY OF RESULTS; SKIN NEOPLASMS; STOMACH NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84946209341     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.3954     Document Type: Article

References (52)

1. Arrowsmith, J. & Miller, P. Trial watch: phase II and phase III attrition rates 2011-2012. Nat. Rev. Drug Discov. 12, 569 (2013).
2. Arrowsmith, J. Trial watch: Phase II failures: 2008-2010. Nat. Rev. Drug Discov. 10, 328-329 (2011).
3. DiMasi, J. A., Reichert, J. M., Feldman, L. & Malins, A. Clinical approval success rates for investigational cancer drugs. Clin. Pharmacol. Ther. 94, 329-335 (2013).
4. Paul, S. M. et al. How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nat. Rev. Drug Discov. 9, 203-214 (2010).
5. Tentler, J. J. et al. Patient-derived tumour xenografts as models for oncology drug development. Nat. Rev. Clin. Oncol. 9, 338-350 (2012).
6. Siolas, D. & Hannon, G. J. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 73, 5315-5319 (2013).
7. Rosfjord, E., Lucas, J., Li, G. & Gerber, H. P. Advances in patient-derived tumor xenografts: from target identification to predicting clinical response rates in oncology. Biochem. Pharmacol. 91, 135-143 (2014).
8. Hidalgo, M. et al. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer Discov. 4, 998-1013 (2014).
9. Bertotti, A. 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. 1, 508-523 (2011).
10. Migliardi, G. 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. 18, 2515-2525 (2012).
11. Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603-607 (2012).
12. DeRose, Y. S. et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat. Med. 17, 1514-1520 (2011).
13. Ding, L. et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464, 999-1005 (2010).
14. Eirew, P. et al. Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution. Nature 518, 422-426 (2015).
15. Hennessey, P. T. et al. Promoter methylation in head and neck squamous cell carcinoma cell lines is significantly different than methylation in primary tumors and xenografts. PLoS ONE 6, e20584 (2011).
16. Julien, S. et al. Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin. Cancer Res. 18, 5314-5328 (2012).
17. Mattie, M. et al. Molecular characterization of patient-derived human pancreatic tumor xenograft models for preclinical and translational development of cancer therapeutics. Neoplasia 15, 1138-1150 (2013).
18. Einarsdottir, B. O. et al. Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions. Oncotarget 5, 9609-9618 (2014).
19. de Plater, L. et al. Establishment and characterisation of a new breast cancer xenograft obtained from a woman carrying a germline BRCA2 mutation. Br. J. Cancer 103, 1192-1200 (2010).
20. Cingolani, P. et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin) 6, 80-92 (2012).
21. Therasse, P. et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl. Cancer Inst. 92, 205-216 (2000).
22. Sosman, J. A. et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N. Engl. J. Med. 366, 707-714 (2012).
23. Ascierto, P. A. et al. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J. Clin. Oncol. 31, 3205-3211 (2013).
24. Kaplan, F. M., Shao, Y., Mayberry, M. M. & Aplin, A. E. Hyperactivation of MEK-ERK1/2 signaling and resistance to apoptosis induced by the oncogenic B-RAF inhibitor, PLX4720, in mutant N-RAS melanoma cells. Oncogene 30, 366-371 (2011).
25. Halaban, R. et al. PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res. 23, 190-200 (2010).
26. Flaherty, K. T. et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N. Engl. J. Med. 367, 1694-1703 (2012).
27. Robert, C. et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N. Engl. J. Med. 372, 30-39 (2015).
28. Shi, H. et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov. 4, 80-93 (2014).
29. Shi, H. et al. Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat. Commun. 3, 724 (2012).
30. Wagle, N. et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 4, 61-68 (2014).
31. Rizos, H. et al. BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin. Cancer Res. 20, 1965-1977 (2014).
32. Papadopoulos, K. P. et al. Unexpected hepatotoxicity in a phase I study of TAS266, a novel tetravalent agonistic nanobody targeting the DR5 receptor. Cancer Chemother. Pharmacol. 75, 887-895 (2015).
33. Fritsch, C. et al. Characterization of the novel and specific PI3K? inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol. Cancer Ther. 13, 1117-1129 (2014).
34. Juric, D. et al. Convergent loss of PTEN leads to clinical resistance to a PI(3)K? inhibitor. Nature 518, 240-244 (2015).
35. Sasai, K. et al. Shh pathway activity is down-regulated in cultured medulloblastoma cells: implications for preclinical studies. Cancer Res. 66, 4215-4222 (2006).
36. Flanigan, S. A. et al. Overcoming IGF1R/IR resistance through inhibition of MEK signaling in colorectal cancer models. Clin. Cancer Res. 19, 6219-6229 (2013).
37. Molina-Arcas, M., Hancock, D. C., Sheridan, C., Kumar, M. S. & Downward, J. Coordinate direct input of both KRAS and IGF1 receptor to activation of PI3 kinase in KRAS-mutant lung cancer. Cancer Discov. 3, 548-563 (2013).
38. Ebi, H. et al. Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers. J. Clin. Invest. 121, 4311-4321 (2011).
39. Friedbichler, K. et al. Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF ligand-neutralizing antibody, and mechanistic rationale for combination with rapamycin. Mol. Cancer Ther. 13, 399-409 (2014).
40. Moran, T. et al. Activity of dalotuzumab, a selective anti-IGF1R antibody, in combination with erlotinib in unselected patients with Non-small-cell lung cancer: a phase I/II randomized trial. Exp. Hematol. Oncol. 3, 26 (2014).
41. Scagliotti, G. V. et al. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann. Oncol 26, 497-504 (2015).
42. Brana, I. et al. A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours. Br. J. Cancer 111, 1932-1944 (2014).
43. Di Cosimo, S. et al. Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: preclinical characterization and phase I clinical trial. Clin. Cancer Res. 21, 49-59 (2015).
44. Das Thakur, M. et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 494, 251-255 (2013).
45. Korpal, M. et al. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov. 3, 1030-1043 (2013).
46. Cerami, E. et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401-404 (2012).
47. Lawrence, M. S. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499, 214-218 (2013).
48. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-1760 (2009).
49. DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491-498 (2011).
50. McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297-1303 (2010).
51. Sathirapongsasuti, J. F. et al. Exome sequencing-based copy-number variation and loss of heterozygosity detection: ExomeCNV. Bioinformatics 27, 2648-2654 (2011).
52. Lehár, J. et al. Synergistic drug combinations tend to improve therapeutically relevant selectivity. Nat. Biotechnol. 27, 659-666 (2009).