Interrogating Open Issues in Cancer Precision Medicine with Patient-derived Xenografts

Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and the implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. This Opinion article discusses aspects of PDX modelling that are relevant to these questions and highlights the merits of shared PDX resources to advance cancer medicine from the perspective of EurOPDX, an international initiative devoted to PDX-based research.

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References

Zimmer L, Barlesi F, Martinez-Garcia M, Dieras V, Schellens J, Spano J . Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations. Clin Cancer Res. 2014; 20(16):4251-61. DOI: 10.1158/1078-0432.CCR-14-0341. View

Murphy B, Yin H, Maris J, Kolb E, Gorlick R, Reynolds C . Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis. Cancer Res. 2016; 76(19):5798-5809. PMC: 5050128. DOI: 10.1158/0008-5472.CAN-16-0122. View

Arrowsmith J, Miller P . Trial watch: phase II and phase III attrition rates 2011-2012. Nat Rev Drug Discov. 2013; 12(8):569. DOI: 10.1038/nrd4090. View

Voloshin T, Gingis-Velitski S, Bril R, Benayoun L, Munster M, Milsom C . G-CSF supplementation with chemotherapy can promote revascularization and subsequent tumor regrowth: prevention by a CXCR4 antagonist. Blood. 2011; 118(12):3426-35. PMC: 3179406. DOI: 10.1182/blood-2010-11-320812. View

Morton J, Bird G, Keysar S, Astling D, Lyons T, Anderson R . XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer. Oncogene. 2015; 35(3):290-300. PMC: 4613815. DOI: 10.1038/onc.2015.94. View

Nguyen L, Cox C, Eirew P, Knapp D, Pellacani D, Kannan N . DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts. Nat Commun. 2014; 5:5871. PMC: 4284657. DOI: 10.1038/ncomms6871. View

Miranda-Lorenzo I, Dorado J, Lonardo E, Alcala S, Serrano A, Clausell-Tormos J . Intracellular autofluorescence: a biomarker for epithelial cancer stem cells. Nat Methods. 2014; 11(11):1161-9. DOI: 10.1038/nmeth.3112. View

Derose Y, Wang G, Lin Y, Bernard P, Buys S, Ebbert M . Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med. 2011; 17(11):1514-20. PMC: 3553601. DOI: 10.1038/nm.2454. View

Schreiber R, Old L, Smyth M . Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. DOI: 10.1126/science.1203486. View

10.

Gao D, Vela I, Sboner A, Iaquinta P, Karthaus W, Gopalan A . Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014; 159(1):176-187. PMC: 4237931. DOI: 10.1016/j.cell.2014.08.016. View

11.

Shultz L, Brehm M, Garcia-Martinez J, Greiner D . Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol. 2012; 12(11):786-98. PMC: 3749872. DOI: 10.1038/nri3311. View

12.

Aggarwal C, Meropol N, Punt C, Iannotti N, Saidman B, Sabbath K . Relationship among circulating tumor cells, CEA and overall survival in patients with metastatic colorectal cancer. Ann Oncol. 2012; 24(2):420-428. DOI: 10.1093/annonc/mds336. View

13.

Zhang X, Claerhout S, Prat A, Dobrolecki L, Petrovic I, Lai Q . A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models. Cancer Res. 2013; 73(15):4885-97. PMC: 3732575. DOI: 10.1158/0008-5472.CAN-12-4081. View

14.

Toyoshima K, Hayashi A, Kashiwagi M, Hayashi N, Iwatsuki M, Ishimoto T . Analysis of circulating tumor cells derived from advanced gastric cancer. Int J Cancer. 2015; 137(4):991-8. DOI: 10.1002/ijc.29455. View

15.

Vincent Jordan N, Bardia A, Wittner B, Benes C, Ligorio M, Zheng Y . HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature. 2016; 537(7618):102-106. PMC: 5161614. DOI: 10.1038/nature19328. View

16.

de Bono J, Ashworth A . Translating cancer research into targeted therapeutics. Nature. 2010; 467(7315):543-9. DOI: 10.1038/nature09339. View

17.

Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty S, Teichmann L . Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol. 2014; 32(4):364-72. PMC: 4017589. DOI: 10.1038/nbt.2858. View

18.

Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C . A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2012; 1(6):508-23. DOI: 10.1158/2159-8290.CD-11-0109. View

19.

Weickhardt A, Price T, Chong G, Gebski V, Pavlakis N, Johns T . Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer. J Clin Oncol. 2012; 30(13):1505-12. DOI: 10.1200/JCO.2011.38.6599. View

20.

Bruna A, Rueda O, Greenwood W, Batra A, Callari M, Batra R . A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds. Cell. 2016; 167(1):260-274.e22. PMC: 5037319. DOI: 10.1016/j.cell.2016.08.041. View