Animal models for modeling pancreatic cancer and novel drug discovery

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7–30. PubMed PMID: 28055103.
   PubMed Web of Science ®Google Scholar
• Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913–2921. PubMed PMID: 24840647.
   PubMed Web of Science ®Google Scholar
• Bisht S, Brossart P, Feldmann G. Current therapeutic options for pancreatic ductal adenocarcinoma. Oncol Res Treat. 2018;41:590–594.
   Web of Science ®Google Scholar
• Behrens D, Walther W, Fichtner I. Pancreatic cancer models for translational research. Pharmacol Ther. 2017 May;173:146–158. PubMed PMID: 28174092.
   PubMed Web of Science ®Google Scholar
• Abolhassani M, Guais A, Sanders E, et al. Screening of well-established drugs targeting cancer metabolism: reproducibility of the efficacy of a highly effective drug combination in mice. Invest New Drugs. 2012 Aug;30(4):1331–1342. PubMed PMID: 21655919.
   PubMed Web of Science ®Google Scholar
• Vallespi MG, Pimentel G, Cabrales-Rico A, et al. Antitumor efficacy, pharmacokinetic and biodistribution studies of the anticancer peptide CIGB-552 in mouse models. J Pept Sci. 2014 Nov;20(11):850–859. PubMed PMID: 25044757.
   PubMed Web of Science ®Google Scholar
• Hingorani SR, Petricoin EF, Maitra A, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003 Dec 1;4(6):437–450. PubMed PMID: 14706336; eng.
   PubMed Web of Science ®Google Scholar
• Hingorani SR, Wang L, Multani AS, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 2005 May 1;7(5):469–483. PubMed PMID: 15894267; eng.
   PubMed Web of Science ®Google Scholar
• Zechner D, Burtin F, Amme J, et al. Characterization of novel carcinoma cell lines for the analysis of therapeutical strategies fighting pancreatic cancer. Cell Biosci. 2015;5:51. PubMed PMID: 26322225; PubMed Central PMCID: PMCPMC4551666.
   PubMed Web of Science ®Google Scholar
• Priebe TS, Atkinson EN, Pan BF, et al. Intrinsic resistance to anticancer agents in the murine pancreatic adenocarcinoma PANC02. Cancer Chemother Pharmacol. 1992;29(6):485–489. PubMed PMID: 1348974.
   PubMed Web of Science ®Google Scholar
• Collignon A, Perles-Barbacaru AT, Robert S, et al. A pancreatic tumor-specific biomarker characterized in humans and mice as an immunogenic onco-glycoprotein is efficient in dendritic cell vaccination. Oncotarget. 2015 Sep 15;6(27):23462–23479. PubMed PMID: 26405163; PubMed Central PMCID: PMCPMC4695130.
   PubMedGoogle Scholar
• Liu Q, Li Y, Niu Z, et al. Atorvastatin (Lipitor) attenuates the effects of aspirin on pancreatic cancerogenesis and the chemotherapeutic efficacy of gemcitabine on pancreatic cancer by promoting M2 polarized tumor associated macrophages. J Exp Clin Cancer Res. 2016 Feb 16;35:33. PubMed PMID: 26879926; PubMed Central PMCID: PMCPMC4754966.
   PubMed Web of Science ®Google Scholar
• Bai Z, Shi Y, Wang J, et al. Multi-modality imaging-monitored creation of rat orthotopic pancreatic head cancer with obstructive jaundice. Oncotarget. 2017 Aug 15;8(33):54277–54284. PubMed PMID: 28903340; PubMed Central PMCID: PMCPMC5589579.
   PubMedGoogle Scholar
• Schutte U, Bisht S, Brossart P, et al. Recent developments of transgenic and xenograft mouse models of pancreatic cancer for translational research. Expert Opin Drug Discov. 2011 Jan;6(1):33–48. PubMed PMID: 22646825.
   PubMed Web of Science ®Google Scholar
• White L, Sterling-Levis K, Kees UR, et al. Medulloblastoma/primitive neuroectodermal tumour studied as a matrigel enhanced subcutaneous xenograft model. J Clin Neurosci. 2001 Mar;8(2):151–156. PubMed PMID: 11484666; eng.
   PubMed Web of Science ®Google Scholar
• van Weerden WM, Romijn JC. Use of nude mouse xenograft models in prostate cancer research. Prostate. 2000 Jun 1;43(4):263–271. PubMed PMID: 10861745; eng.
   PubMed Web of Science ®Google Scholar
• Mueller BM, Reisfeld RA. Potential of the scid mouse as a host for human tumors. Cancer Metastasis Rev. 1991 Oct;10(3):193–200. PubMed PMID: 1764764; eng.
   PubMed Web of Science ®Google Scholar
• Maitra A, Hruban RH. Pancreatic cancer. Annu Rev Pathol. 2008 Jan 1;3:157–188. PubMed PMID: 18039136; eng.
   PubMed Web of Science ®Google Scholar
• Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26;321(5897):1801–1806. PubMed PMID: 18772397; PubMed Central PMCID: PMC2848990. eng.
   PubMed Web of Science ®Google Scholar
• Perales-Paton J, Pineiro-Yanez E, Tejero H, et al. Pancreas cancer precision treatment using avatar mice from a bioinformatics perspective. Public Health Genomics. 2017;20(2):81–91. PubMed PMID: 28858862.
   PubMed Web of Science ®Google Scholar
• Kamiyama H, Kamiyama M, Hong SM, et al. In vivo and in vitro propagation of intraductal papillary mucinous neoplasms. Lab Invest. 2010 May;90(5):665–673. PubMed PMID: 20231822; PubMed Central PMCID: PMC2885280. eng.
   PubMed Web of Science ®Google Scholar
• Rubio-Viqueira B, Jimeno A, Cusatis G, et al. An in vivo platform for translational drug development in pancreatic cancer. Clin Cancer Res. 2006 Aug 1;12(15):4652–4661. PubMed PMID: 16899615; eng.
   PubMed Web of Science ®Google Scholar
• Jimeno A, Feldmann G, Suarez-Gauthier A, et al. A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development. Mol Cancer Ther. 2009 Feb;8(2):310–314. PubMed PMID: 19174553; eng.
   PubMed Web of Science ®Google Scholar
• Winnard PT Jr., Pathak AP, Dhara S, et al. Molecular imaging of metastatic potential. J Nucl Med. 2008 Jun;49 Suppl 2:96S–112S. PubMed PMID: 18523068; PubMed Central PMCID: PMCPMC5516907.
   PubMed Web of Science ®Google Scholar
• Foss CA, Fox JJ, Feldmann G, et al. Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer. Mol Imaging. 2007 Mar-Apr;6(2):131–139. PubMed PMID: 17445507.
   PubMed Web of Science ®Google Scholar
• Tran Cao HS, Reynoso J, Yang M, et al. Development of the transgenic cyan fluorescent protein (CFP)-expressing nude mouse for “Technicolor” cancer imaging. J Cell Biochem. 2009 May 15;107(2):328–334. PubMed PMID: 19306297; PubMed Central PMCID: PMCPMC2833326.
   PubMed Web of Science ®Google Scholar
• Zhou J, Yu Z, Zhao S, et al. Lentivirus-based DsRed-2-transfected pancreatic cancer cells for deep in vivo imaging of metastatic disease. J Surg Res. 2009 Nov;157(1):63–70. PubMed PMID: 19589544.
   PubMed Web of Science ®Google Scholar
• Feldmann G, Dhara S, Fendrich V, et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res. 2007 Mar 1;67(5):2187–2196. PubMed PMID: 17332349; eng.
   PubMed Web of Science ®Google Scholar
• Lin TJ, Beal KM, DeGruttola HS, et al. Utilization of sequence variants as biomarkers to analyze population dynamics in cloned cell lines. Biotechnol Bioeng. 2017 Aug;114(8):1744–1752. PubMed PMID: 28369783.
   PubMed Web of Science ®Google Scholar
• Reiter JG, Makohon-Moore AP, Gerold JM, et al. Minimal functional driver gene heterogeneity among untreated metastases. Science. 2018 Sep 7;361(6406):1033–1037. PubMed PMID: 30190408.
   PubMed Web of Science ®Google Scholar
• Horbach S, Halffman W. The ghosts of HeLa: how cell line misidentification contaminates the scientific literature. PLoS One. 2017;12(10):e0186281. PubMed PMID: 29023500; PubMed Central PMCID: PMCPMC5638414.
   PubMed Web of Science ®Google Scholar
• Vaughan L, Glanzel W, Korch C, et al. Widespread use of misidentified cell line KB (HeLa): incorrect attribution and its impact revealed through mining the scientific literature. Cancer Res. 2017 Jun 1;77(11):2784–2788. PubMed PMID: 28455420.
   PubMed Web of Science ®Google Scholar
• Otto R, Sers C, Leser U. Robust in-silico identification of cancer cell lines based on next generation sequencing. Oncotarget. 2017 May 23;8(21):34310–34320. PubMed PMID: 28415721; PubMed Central PMCID: PMCPMC5470969.
   PubMedGoogle Scholar
• von Ahrens D, Bhagat TD, Nagrath D, et al. The role of stromal cancer-associated fibroblasts in pancreatic cancer. J Hematol Oncol. 2017 Mar 28;10(1):76. PubMed PMID: 28351381; PubMed Central PMCID: PMCPMC5371211.
   PubMedGoogle Scholar
• Cho SY, Kang W, Han JY, et al. An integrative approach to precision cancer medicine using patient-derived xenografts. Mol Cells. 2016 Feb;39(2):77–86. PubMed PMID: 26831452; PubMed Central PMCID: PMCPMC4757806.
   PubMed Web of Science ®Google Scholar
• Garrido-Laguna I, Uson M, Rajeshkumar NV, et al. Tumor engraftment in nude mice and enrichment in stroma- related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer. Clin Cancer Res. 2011 Sep 1;17(17):5793–5800. PubMed PMID: 21742805; PubMed Central PMCID: PMCPMC3210576.
   PubMed Web of Science ®Google Scholar
• Tentler JJ, Tan AC, Weekes CD, et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol. 2012 Apr 17;9(6):338–350. PubMed PMID: 22508028; PubMed Central PMCID: PMCPMC3928688.
   PubMed Web of Science ®Google Scholar
• Walters DM, Stokes JB, Adair SJ, et al. Clinical, molecular and genetic validation of a murine orthotopic xenograft model of pancreatic adenocarcinoma using fresh human specimens. PLoS One. 2013;8(10):e77065. PubMed PMID: 24204737; PubMed Central PMCID: PMCPMC3799939.
   PubMed Web of Science ®Google Scholar
• Jung J, Lee CH, Seol HS, et al. Generation and molecular characterization of pancreatic cancer patient-derived xenografts reveals their heterologous nature. Oncotarget. 2016 Sep 20;7(38):62533–62546. PubMed PMID: 27613834; PubMed Central PMCID: PMCPMC5308744.
   PubMedGoogle Scholar
• Thomas RM, Truty MJ, Kim M, et al. The canary in the coal mine: the growth of patient-derived tumorgrafts in mice predicts clinical recurrence after surgical resection of pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2015;22(6):1884–1892. PubMed PMID: 25404477; PubMed Central PMCID: PMCPMC5274872.
   PubMed Web of Science ®Google Scholar
• 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 Sep;80(9):873–877. PubMed PMID: 25197873; PubMed Central PMCID: PMCPMC4425299.
   PubMed Web of Science ®Google Scholar
• Damhofer H, Ebbing EA, Steins A, et al. Establishment of patient-derived xenograft models and cell lines for malignancies of the upper gastrointestinal tract. J Transl Med. 2015 Apr 11;13:115. PubMed PMID: 25884700; PubMed Central PMCID: PMCPMC4419410.
   PubMed Web of Science ®Google Scholar
• Kamiyama H, Rauenzahn S, Shim JS, et al. Personalized chemotherapy profiling using cancer cell lines from selectable mice. Clin Cancer Res. 2013 Mar 1;19(5):1139–1146. PubMed PMID: 23340293; PubMed Central PMCID: PMCPMC3612923.
   PubMed Web of Science ®Google Scholar
• Gao H, Korn JM, Ferretti S, et al. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response. Nat Med. 2015 Nov;21(11):1318–1325. PubMed PMID: 26479923.
   PubMed Web of Science ®Google Scholar
• Hodgkinson CL, Morrow CJ, Li Y, et al. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med. 2014 Aug;20(8):897–903. PubMed PMID: 24880617.
   PubMed Web of Science ®Google Scholar
• Allaway RJ, Fischer DA, de Abreu FB, et al. Genomic characterization of patient-derived xenograft models established from fine needle aspirate biopsies of a primary pancreatic ductal adenocarcinoma and from patient-matched metastatic sites. Oncotarget. 2016 Mar 29;7(13):17087–17102. PubMed PMID: 26934555; PubMed Central PMCID: PMCPMC4941373.
   PubMedGoogle Scholar
• Murphy B, Yin H, Maris JM, et al. Evaluation of alternative in vivo drug screening methodology: a single mouse analysis. Cancer Res. 2016 Oct 1;76(19):5798–5809. PubMed PMID: 27496711; PubMed Central PMCID: PMCPMC5050128.
   PubMed Web of Science ®Google Scholar
• Von Hoff DD, Ramanathan RK, Borad MJ, et al. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548–4554. PubMed PMID: 21969517; PubMed Central PMCID: PMCPMC3565012.
   PubMed Web of Science ®Google Scholar
• Laheru D, Shah P, Rajeshkumar NV, et al. Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic acid (FTS, Salirasib) in pancreatic cancer. Invest New Drugs. 2012 Dec;30(6):2391–2399. PubMed PMID: 22547163; PubMed Central PMCID: PMCPMC3557459.
   PubMed Web of Science ®Google Scholar
• Morton JJ, Bird G, Refaeli Y, et al. Humanized mouse xenograft models: narrowing the tumor-microenvironment gap. Cancer Res. 2016 Nov 1;76(21):6153–6158. PubMed PMID: 27587540; PubMed Central PMCID: PMCPMC5093075.
   PubMed Web of Science ®Google Scholar
• Morton JJ, Keysar SB, Perrenoud L, et al. Dual use of hematopoietic and mesenchymal stem cells enhances engraftment and immune cell trafficking in an allogeneic humanized mouse model of head and neck cancer. Mol Carcinog. 2018 Aug 21;57:1651–1663. PubMed PMID: 30129680.
   PubMed Web of Science ®Google Scholar
• Wulf-Goldenberg A, Eckert K, Fichtner I. Intrahepatically transplanted human cord blood cells reduce SW480 tumor growth in the presence of bispecific EpCAM/CD3 antibody. Cytotherapy. 2011 Jan;13(1):108–113. PubMed PMID: 20839999.
   PubMed Web of Science ®Google Scholar
• Wulf-Goldenberg A, Keil M, Fichtner I, et al. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment. Tissue Cell. 2012 Apr;44(2):80–86. PubMed PMID: 22197619.
   PubMed Web of Science ®Google Scholar
• Holzapfel BM, Wagner F, Thibaudeau L, et al. Concise review: humanized models of tumor immunology in the 21st century: convergence of cancer research and tissue engineering. Stem Cells. 2015 Jun;33(6):1696–1704. PubMed PMID: 25694194.
   PubMed Web of Science ®Google Scholar
• Guichelaar T, Emmelot ME, Rozemuller H, et al. Human regulatory T cells do not suppress the antitumor immunity in the bone marrow: a role for bone marrow stromal cells in neutralizing regulatory T cells. Clin Cancer Res. 2013 Mar 15;19(6):1467–1475. PubMed PMID: 23382115.
   PubMed Web of Science ®Google Scholar
• Baker LA, Tuveson DA. Generation and culture of tumor and metastatic organoids from murine models of pancreatic ductal adenocarcinoma. Methods Mol Biol. 2019;1882:117–133. PubMed PMID: 30378048.
   PubMedGoogle Scholar
• Baker LA, Tiriac H, Tuveson DA. Generation and culture of human pancreatic ductal adenocarcinoma organoids from resected tumor specimens. Methods Mol Biol. 2019;1882:97–115. PubMed PMID: 30378047.
   PubMedGoogle Scholar
• Boj SF, Hwang CI, Baker LA, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015 Jan 15;160(1–2):324–338. PubMed PMID: 25557080; PubMed Central PMCID: PMCPMC4334572.
   PubMed Web of Science ®Google Scholar
• Huang L, Holtzinger A, Jagan I, et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat Med. 2015 Nov;21(11):1364–1371. PubMed PMID: 26501191; PubMed Central PMCID: PMCPMC4753163.
   PubMed Web of Science ®Google Scholar
• Li X, Nadauld L, Ootani A, et al. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat Med. 2014 Jul;20(7):769–777. PubMed PMID: 24859528; PubMed Central PMCID: PMCPMC4087144.
   PubMed Web of Science ®Google Scholar
• Tiriac H, Belleau P, Engle DD, et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov. 2018 Sep 8;8(9):1112–1129. PubMed PMID: 29853643; PubMed Central PMCID: PMCPMC6125219.
   PubMed Web of Science ®Google Scholar
• Seino T, Kawasaki S, Shimokawa M, et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell. 2018 Mar 1;22(3):454–467 e6. PubMed PMID: 29337182.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Electronic address aadhe, cancer genome atlas research N. Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell. 2017 Aug 14;32(2):185–203 e13. PubMed PMID: 28810144; PubMed Central PMCID: PMCPMC5964983.
   PubMed Web of Science ®Google Scholar
• Bardeesy N, Aguirre AJ, Chu GC, et al. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5947–5952. PubMed PMID: 16585505; PubMed Central PMCID: PMC1458678. eng.
   PubMed Web of Science ®Google Scholar
• Aguirre AJ, Bardeesy N, Sinha M, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 2003 Dec 15;17(24):3112–3126. PubMed PMID: 14681207; eng.
   PubMed Web of Science ®Google Scholar
• Jonsson J, Carlsson L, Edlund T, et al. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature. 1994 Oct 13;371(6498):606–609. PubMed PMID: 7935793; eng.
   PubMed Web of Science ®Google Scholar
• Krapp A, Knofler M, Ledermann B, et al. The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes Dev. 1998 Dec 1;12(23):3752–3763. PubMed PMID: 9851981; PubMed Central PMCID: PMC317250. eng.
   PubMed Web of Science ®Google Scholar
• Sausville EA, Elsayed Y, Monga M, et al. Signal transduction–directed cancer treatments. Annu Rev Pharmacol Toxicol. 2003;43:199–231. PubMed PMID: 12195027.
   PubMed Web of Science ®Google Scholar
• Feldmann G, Beaty R, Hruban RH, et al. Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pancreat Surg. 2007;14(3):224–232. PubMed PMID: 17520196; PubMed Central PMCID: PMCPMC2666331.
   PubMedGoogle Scholar
• Bardeesy N, Sharpless NE. RAS unplugged: negative feedback and oncogene-induced senescence. Cancer Cell. 2006 Dec;10(6):451–453. PubMed PMID: 17157783; eng.
   PubMed Web of Science ®Google Scholar
• Javle M, Golan T, Maitra A. Changing the course of pancreatic cancer – focus on recent translational advances. Cancer Treat Rev. 2016 Mar;44:17–25. PubMed PMID: 26924195.
   PubMed Web of Science ®Google Scholar
• Janes MR, Zhang J, Li LS, et al. Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor. Cell. 2018 Jan 25;172(3):578–589 e17. PubMed PMID: 29373830.
   PubMed Web of Science ®Google Scholar
• Furuse J, Kurata T, Okano N, et al. An early clinical trial of Salirasib, an oral RAS inhibitor, in Japanese patients with relapsed/refractory solid tumors. Cancer Chemother Pharmacol. 2018 Jul 10;82:511–519. PubMed PMID: 29992354.
   Web of Science ®Google Scholar
• Ying H, Kimmelman AC, Lyssiotis CA, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 2012 Apr 27;149(3):656–670. PubMed PMID: 22541435; PubMed Central PMCID: PMCPMC3472002.
   PubMed Web of Science ®Google Scholar
• Viale A, Pettazzoni P, Lyssiotis CA, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014 Oct 30;514(7524):628–632. PubMed PMID: 25119024; PubMed Central PMCID: PMCPMC4376130.
   PubMed Web of Science ®Google Scholar
• Muzumdar MD, Chen PY, Dorans KJ, et al. Survival of pancreatic cancer cells lacking KRAS function. Nat Commun. 2017 Oct 23;8(1):1090. PubMed PMID: 29061961; PubMed Central PMCID: PMCPMC5653666.
   PubMedGoogle Scholar
• Feldmann G, Mishra A, Bisht S, et al. Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models. Cancer Biol Ther. 2011 Oct 1;12(7):598–609. PubMed PMID: 21768779; PubMed Central PMCID: PMCPMC3218385.
   PubMed Web of Science ®Google Scholar
• Feldmann G, Mishra A, Hong SM, et al. Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression through the suppression of Ras-Ral signaling. Cancer Res. 2010 Jun 1;70(11):4460–4469. PubMed PMID: 20484029; PubMed Central PMCID: PMCPMC3071300.
   PubMed Web of Science ®Google Scholar
• Vandamme T, Beyens M, de Beeck KO, et al. Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors. Br J Cancer. 2016 Mar 15;114(6):650–658. PubMed PMID: 26978006; PubMed Central PMCID: PMCPMC4800296.
   PubMed Web of Science ®Google Scholar
• Akinleye A, Iragavarapu C, Furqan M, et al. Novel agents for advanced pancreatic cancer. Oncotarget. 2015 Nov 24;6(37):39521–39537. PubMed PMID: 26369833; PubMed Central PMCID: PMCPMC4741843.
   PubMedGoogle Scholar
• Bisht S, Feldmann G. Novel targets in pancreatic cancer therapy. Oncol Res Treat. 2018;41. DOI:10.1159/000493437
   Google Scholar
• Habbe N, Shi G, Meguid RA, et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18913–18918. PubMed PMID: 19028870; PubMed Central PMCID: PMCPMC2596215.
   PubMed Web of Science ®Google Scholar
• Schonhuber N, Seidler B, Schuck K, et al. A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer. Nat Med. 2014 Nov;20(11):1340–1347. PubMed PMID: 25326799; PubMed Central PMCID: PMCPMC4270133.
   PubMed Web of Science ®Google Scholar
• Frese KK, Neesse A, Cook N, et al. nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov. 2012 Mar;2(3):260–269. PubMed PMID: 22585996; PubMed Central PMCID: PMCPMC4866937.
   PubMed Web of Science ®Google Scholar
• Yip-Schneider MT, Wu H, Stantz K, et al. Dimethylaminoparthenolide and gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer. BMC Cancer. 2013 Apr 17;13:194. PubMed PMID: 23590467; PubMed Central PMCID: PMCPMC3672012.
   PubMed Web of Science ®Google Scholar
• Ocal O, Pashkov V, Kollipara RK, et al. A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics. Dis Model Mech. 2015 Oct 1;8(10):1201–1211. PubMed PMID: 26438693; PubMed Central PMCID: PMCPMC4610235.
   PubMed Web of Science ®Google Scholar
• Maresch R, Mueller S, Veltkamp C, et al. Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR/Cas9 delivery in mice. Nat Commun. 2016 Feb 26;7:10770. PubMed PMID: 26916719; PubMed Central PMCID: PMCPMC4773438.
   PubMed Web of Science ®Google Scholar
• Majumder K, Arora N, Modi S, et al. A novel immunocompetent mouse model of pancreatic cancer with robust stroma: a valuable tool for preclinical evaluation of new therapies. J Gastrointest Surg. 2016 Jan;20(1):53–65; discussion 65. PubMed PMID: 26582596; PubMed Central PMCID: PMCPMC5724755.
   Web of Science ®Google Scholar
• Grippo PJ, Sandgren EP. Modeling pancreatic cancer in animals to address specific hypotheses. Methods Mol Med. 2005;103:217–243. PubMed PMID: 15542910.
   PubMedGoogle Scholar
• Schaeffer BK, Zurlo J, Longnecker DS. Activation of c-Ki-ras not detectable in adenomas or adenocarcinomas arising in rat pancreas. Mol Carcinog. 1990;3(3):165–170. PubMed PMID: 2196902.
   PubMed Web of Science ®Google Scholar
• Rivera JA, Graeme-Cook F, Werner J, et al. A rat model of pancreatic ductal adenocarcinoma: targeting chemical carcinogens. Surgery. 1997 Jul;122(1):82–90. PubMed PMID: 9225919.
   PubMed Web of Science ®Google Scholar
• Dissin J, Mills LR, Mains DL, et al. Experimental induction of pancreatic adenocarcinoma in rats. J Natl Cancer Inst. 1975 Oct;55(4):857–864. PubMed PMID: 810597.
   PubMedGoogle Scholar
• Bockman DE, Black O Jr., Mills LR, et al. Fine structure of pancreatic adenocarcinoma induced in rats by 7,12-dimethylbenz(a)anthracene. J Natl Cancer Inst. 1976 Oct;57(4):931–936. PubMed PMID: 187782.
   PubMedGoogle Scholar
• Gingell R, Wallcave L, Nagel D, et al. Metabolism of the pancreatic carcinogens N-nitroso-bis(2-oxopropyl)amine and N-nitroso-bis(2-hydroxypropyl)amine in the Syrian hamster. J Natl Cancer Inst. 1976 Nov;57(5):1175–1178. PubMed PMID: 1003547.
   PubMedGoogle Scholar
• Pour P, Althoff J. The effect of N-nitrosobis(2-oxopropyl)amine after oral administration to hamsters. Cancer Lett. 1977 May;2(6):323–326. PubMed PMID: 193628.
   PubMed Web of Science ®Google Scholar
• Konishi Y, Tsutsumi M, Tsujiuchi T. Mechanistic analysis of pancreatic ductal carcinogenesis in hamsters. Pancreas. 1998 Apr;16(3):300–306. PubMed PMID: 9548670.
   PubMed Web of Science ®Google Scholar
• Flaks B, Moore MA, Flaks A. Ultrastructural analysis of pancreatic carcinogenesis. V. Changes in differentiation of acinar cells during chronic treatment with N-nitrosobis(2-hydroxypropyl)amine. Carcinogenesis. 1982;3(5):485–498. PubMed PMID: 7094210.
   PubMed Web of Science ®Google Scholar
• Feng Z, Hu W, Chen JX, et al. Preferential DNA damage and poor repair determine ras gene mutational hotspot in human cancer. J Natl Cancer Inst. 2002 Oct 16;94(20):1527–1536. PubMed PMID: 12381705.
   PubMedGoogle Scholar
• Erill N, Cuatrecasas M, Sancho FJ, et al. K-ras and p53 mutations in hamster pancreatic ductal adenocarcinomas and cell lines. Am J Pathol. 1996 Oct;149(4):1333–1339. PubMed PMID: 8863680; PubMed Central PMCID: PMCPMC1865186.
   PubMed Web of Science ®Google Scholar
• Flaks B, Moore MA, Flaks A. Ultrastructural analysis of pancreatic carcinogenesis. IV. Pseudoductular transformation of acini in the hamster pancreas during N-nitroso-bis(2-hydroxypropyl)amine carcinogenesis. Carcinogenesis. 1981;2(12):1241–1253. PubMed PMID: 7326824.
   PubMed Web of Science ®Google Scholar
• Flaks B, Moore MA, Flaks A. Ultrastructural analysis of pancreatic carcinogenesis. VI. Early changes in hamster acinar cells induced by N-nitroso-bis(2-hydroxypropyl)amine. Carcinogenesis. 1982;3(9):1063–1070. PubMed PMID: 7139863.
   PubMed Web of Science ®Google Scholar
• Fendrich V, Jendryschek F, Beeck S, et al. Genetic and pharmacologic abrogation of Snail1 inhibits acinar-to-ductal metaplasia in precursor lesions of pancreatic ductal adenocarcinoma and pancreatic injury. Oncogene. 2018 Apr;37(14):1845–1856. PubMed PMID: 29367759.
   PubMed Web of Science ®Google Scholar
• He P, Yang JW, Yang VW, et al. Kruppel-like factor 5, increased in pancreatic ductal adenocarcinoma, promotes proliferation, acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia, and tumor growth in mice. Gastroenterology. 2018 Apr;154(5):1494–1508 e13. PubMed PMID: 29248441; PubMed Central PMCID: PMCPMC5880723.
   PubMed Web of Science ®Google Scholar
• Liu S, Leach SD. Zebrafish models for cancer. Annu Rev Pathol. 2011;6:71–93. PubMed PMID: 21261518.
   PubMed Web of Science ®Google Scholar
• Amatruda JF, Shepard JL, Stern HM, et al. Zebrafish as a cancer model system. Cancer Cell. 2002 Apr;1(3):229–231. PubMed PMID: 12086858.
   PubMed Web of Science ®Google Scholar
• Streisinger G, Walker C, Dower N, et al. Production of clones of homozygous diploid zebra fish (Brachydanio rerio). Nature. 1981 May 28;291(5813):293–296. PubMed PMID: 7248006.
   PubMed Web of Science ®Google Scholar
• Driever W, Solnica-Krezel L, Schier AF, et al. A genetic screen for mutations affecting embryogenesis in zebrafish. Development. 1996 Dec;123:37–46. PubMed PMID: 9007227.
   PubMed Web of Science ®Google Scholar
• Mullins MC, Hammerschmidt M, Kane DA, et al. Genes establishing dorsoventral pattern formation in the zebrafish embryo: the ventral specifying genes. Development. 1996 Dec;123:81–93. PubMed PMID: 9007231.
   PubMed Web of Science ®Google Scholar
• Park SW, Davison JM, Rhee J, et al. Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas. Gastroenterology. 2008 Jun;134(7):2080–2090. PubMed PMID: 18549880; PubMed Central PMCID: PMCPMC2654247.
   PubMed Web of Science ®Google Scholar
• Liu S, Leach SD. Screening pancreatic oncogenes in zebrafish using the Gal4/UAS system. Methods Cell Biol. 2011;105:367–381. PubMed PMID: 21951538; PubMed Central PMCID: PMCPMC3910423.
   PubMed Web of Science ®Google Scholar
• Guo M, Wei H, Hu J, et al. U0126 inhibits pancreatic cancer progression via the KRAS signaling pathway in a zebrafish xenotransplantation model. Oncol Rep. 2015 Aug;34(2):699–706. PubMed PMID: 26035715.
   PubMed Web of Science ®Google Scholar
• Marques IJ, Weiss FU, Vlecken DH, et al. Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model. BMC Cancer. 2009 Apr 28;9:128. PubMed PMID: 19400945; PubMed Central PMCID: PMCPMC2697170.
   PubMed Web of Science ®Google Scholar
• D’Amico S, Shi J, Martin BL, et al. STAT3 is a master regulator of epithelial identity and KRAS-driven tumorigenesis. Genes Dev. 2018 Sep 1;32(17–18):1175–1187. PubMed PMID: 30135074; PubMed Central PMCID: PMCPMC6120712.
   PubMed Web of Science ®Google Scholar
• Bardeesy N, Cheng KH, Berger JH, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 2006 Nov 15;20(22):3130–3146. PubMed PMID: 17114584; PubMed Central PMCID: PMC1635148. eng.
   PubMed Web of Science ®Google Scholar
• Izeradjene K, Combs C, Best M, et al. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell. 2007 Mar;11(3):229–243. PubMed PMID: 17349581; eng.
   PubMed Web of Science ®Google Scholar
• Ijichi H, Chytil A, Gorska AE, et al. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev. 2006 Nov 15;20(22):3147–3160. PubMed PMID: 17114585; PubMed Central PMCID: PMC1635149. eng.
   PubMed Web of Science ®Google Scholar
• Kojima K, Vickers SM, Adsay NV, et al. Inactivation of Smad4 accelerates Kras(G12D)-mediated pancreatic neoplasia. Cancer Res. 2007 Sep 1;67(17):8121–8130. PubMed PMID: 17804724.
   PubMed Web of Science ®Google Scholar
• Muller-Decker K, Furstenberger G, Annan N, et al. Preinvasive duct-derived neoplasms in pancreas of keratin 5-promoter cyclooxygenase-2 transgenic mice. Gastroenterology. 2006 Jun;130(7):2165–2178. PubMed PMID: 16762637; eng.
   PubMed Web of Science ®Google Scholar
• Furukawa T, Kuboki Y, Tanji E, et al. Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep. 2011;1:161. PubMed PMID: 22355676; PubMed Central PMCID: PMCPMC3240977.
   PubMed Web of Science ®Google Scholar
• Kanda M, Matthaei H, Wu J, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology. 2012 Apr;142(4):730–733 e9. PubMed PMID: 22226782; PubMed Central PMCID: PMCPMC3321090.
   PubMed Web of Science ®Google Scholar
• Wu J, Matthaei H, Maitra A, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med. 2011 Jul 20;3(92):92ra66. PubMed PMID: 21775669; PubMed Central PMCID: PMCPMC3160649.
   PubMed Web of Science ®Google Scholar
• Ideno N, Yamaguchi H, Ghosh B, et al. GNAS(R201C) induces pancreatic cystic neoplasms in mice that express activated KRAS by inhibiting YAP1 signaling. Gastroenterology. 2018 Aug 21;155:1593–1607.e12. PubMed PMID: 30142336.
   PubMed Web of Science ®Google Scholar
• Hezel AF, Gurumurthy S, Granot Z, et al. Pancreatic LKB1 deletion leads to acinar polarity defects and cystic neoplasms. Mol Cell Biol. 2008 Apr;28(7):2414–2425. PubMed PMID: 18227155; PubMed Central PMCID: PMCPMC2268441.
   PubMed Web of Science ®Google Scholar
• Granot Z, Swisa A, Magenheim J, et al. LKB1 regulates pancreatic beta cell size, polarity, and function. Cell Metab. 2009 Oct;10(4):296–308. PubMed PMID: 19808022; PubMed Central PMCID: PMCPMC2790403.
   PubMed Web of Science ®Google Scholar
• Morton JP, Jamieson NB, Karim SA, et al. LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology. 2010 Aug;139(2):586–597, 597 e1-6. PubMed PMID: 20452353; PubMed Central PMCID: PMCPMC3770904.
   Web of Science ®Google Scholar
• Schmitt A, Reinhardt HC, Zander T, et al. Targeting defects in the cellular dna damage response for the treatment of pancreatic ductal adenocarcinoma. Oncol Res Treat. 2018;41:619–625.
   PubMed Web of Science ®Google Scholar
• Feldmann G, Karikari C, Dal Molin M, et al. Inactivation of Brca2 cooperates with Trp53(R172H) to induce invasive pancreatic ductal adenocarcinomas in mice: a mouse model of familial pancreatic cancer. Cancer Biol Ther. 2011 Jun 1;11(11):959–968. PubMed PMID: 21455033; PubMed Central PMCID: PMCPMC3127047.
   PubMed Web of Science ®Google Scholar
• Skoulidis F, Cassidy LD, Pisupati V, et al. Germline Brca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell. 2010 Nov 16;18(5):499–509. PubMed PMID: 21056012.
   PubMed Web of Science ®Google Scholar
• Rowley M, Ohashi A, Mondal G, et al. Inactivation of Brca2 promotes Trp53-associated but inhibits KrasG12D-dependent pancreatic cancer development in mice. Gastroenterology. 2011 Apr;140(4):1303–1313 e1-3. PubMed PMID: 21199651; PubMed Central PMCID: PMCPMC3066280.
   PubMed Web of Science ®Google Scholar
• Perkhofer L, Schmitt A, Romero Carrasco MC, et al. ATM deficiency generating genomic instability sensitizes pancreatic ductal adenocarcinoma cells to therapy-induced DNA damage. Cancer Res. 2017 Oct 15;77(20):5576–5590. PubMed PMID: 28790064.
   PubMed Web of Science ®Google Scholar
• Berman DM, Karhadkar SS, Maitra A, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003 Oct 23;425(6960):846–851. PubMed PMID: 14520411; eng.
   PubMed Web of Science ®Google Scholar
• Thayer SP, Di Magliano MP, Heiser PW, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003 Oct 23;425(6960):851–856. PubMed PMID: 14520413; eng.
   PubMed Web of Science ®Google Scholar
• Feldmann G, Fendrich V, McGovern K, et al. An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Mol Cancer Ther. 2008 Sep;7(9):2725–2735. PubMed PMID: 18790753; PubMed Central PMCID: PMC2605523. eng.
   PubMed Web of Science ®Google Scholar
• Pasca Di Magliano M, Sekine S, Ermilov A, et al. Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev. 2006 Nov 15;20(22):3161–3173. PubMed PMID: 17114586; PubMed Central PMCID: PMCPMC1635150.
   PubMed Web of Science ®Google Scholar
• Hruban RH, Adsay NV, Albores-Saavedra J, et al. Pathology of genetically engineered mouse models of pancreatic exocrine cancer: consensus report and recommendations. Cancer Res. 2006 Jan 1;66(1):95–106. PubMed PMID: 16397221; eng.
   PubMed Web of Science ®Google Scholar
• Fendrich V, Oh E, Bang S, et al. Ectopic overexpression of Sonic Hedgehog (Shh) induces stromal expansion and metaplasia in the adult murine pancreas. Neoplasia. 2011 Oct;13(10):923–930. PubMed PMID: 22028618; PubMed Central PMCID: PMCPMC3201569.
   PubMed Web of Science ®Google Scholar
• Gopinathan A, Morton JP, Jodrell DI, et al. GEMMs as preclinical models for testing pancreatic cancer therapies. Dis Model Mech. 2015 Oct 1;8(10):1185–1200. PubMed PMID: 26438692; PubMed Central PMCID: PMCPMC4610236.
   PubMed Web of Science ®Google Scholar
• Gades NM, Ohash A, Mills LD, et al. Spontaneous vulvar papillomas in a colony of mice used for pancreatic cancer research. Comp Med. 2008 Jun;58(3):271–275. PubMed PMID: 18589869; PubMed Central PMCID: PMCPMC2704118.
   PubMed Web of Science ®Google Scholar
• Logsdon CD, Arumugam T, Ramachandran V. Animal models of gastrointestinal and liver diseases. The difficulty of animal modeling of pancreatic cancer for preclinical evaluation of therapeutics. Am J Physiol Gastrointest Liver Physiol. 2015 Sep 1;309(5):G283–G291. PubMed PMID: 26159697; PubMed Central PMCID: PMCPMC4556944.
   PubMed Web of Science ®Google Scholar
• Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013 Dec 20;342(6165):1432–1433. PubMed PMID: 24357284.
   PubMed Web of Science ®Google Scholar
• Brudno JN, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for lymphoma. Nat Rev Clin Oncol. 2018 Jan;15(1):31–46. PubMed PMID: 28857075.
   PubMed Web of Science ®Google Scholar