Mouse Models of Pancreatic Exocrine Cancer

  • Michelle Lockley
  • David Tuveson
Reference work entry


Pancreatic ductal adenocarcinoma (PDA) is a common and lethal disease. Despite the prevalence of PDA, our understanding of the critical events underlying disease pathogenesis and therapeutic resistance is woefully inadequate. To accelerate progress, much effort has been directed at recapitulating PDA in suitable animal models. Early efforts to model PDA in rodents utilized chemical carcinogenesis, and although useful for certain applications, crucial limitations prevented their widespread utility. Traditional transgenic approaches also failed to produce accurate models of pancreatic cancer in mice, potentially due to the non-physiological control of gene expression. The advent of gene targeting in embryonic stem cells and a deeper understanding of the molecular and cellular events that occur during pancreatic neoplasia enabled the development of accurate models of pre-invasive and invasive PDA. Such models are now yielding fruitful information of direct relevance to patients with pancreatic cancer.


Pancreatic Cancer Acinar Cell Pancreatic Ductal Adenocarcinoma Human Pancreatic Cancer Intraductal Papillary Mucinous Neoplasm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    CancerStats: Pancreatic cancer-UK. Cancer Research UK. 2006.
  2. 2.
    Mueller MM, Fusenig NE: Friends or foes - bipolar effects of the tumour stroma in cancer. Nature Rev 2004;4:839–849.Google Scholar
  3. 3.
    Frese KK, Tuveson DA: Maximizing mouse cancer models. Nat Rev 2007;7:645–658.CrossRefGoogle Scholar
  4. 4.
    Caldas C, Kern SE: K-ras mutation and pancreatic adenocarcinoma. Int J Pancreatol 1995;18:1–6.PubMedGoogle Scholar
  5. 5.
    Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988;53:549–554.CrossRefPubMedGoogle Scholar
  6. 6.
    Hilgers W, Kern SE: Molecular genetic basis of pancreatic adenocarcinoma. Genes Chromosomes Cancer 1999;26:1–12.CrossRefPubMedGoogle Scholar
  7. 7.
    Maitra A, Hruban RH: Pancreatic cancer. Annual Rev Pathol 2008;3:157–188.CrossRefGoogle Scholar
  8. 8.
    Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK, Moskaluk CA, Hahn SA, Schwarte-Waldhoff I, Schmiegel W, et al.: Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res 1997;57:3126–3130.PubMedGoogle Scholar
  9. 9.
    Redston MS, Caldas C, Seymour AB, Hruban RH, da Costa L, Yeo CJ, Kern SE: p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Res 1994;54:3025–3033.PubMedGoogle Scholar
  10. 10.
    Rozenblum E, Schutte M, Goggins M, Hahn SA, Panzer S, Zahurak M, Goodman SN, Sohn TA, Hruban RH, Yeo CJ, Kern SE: Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res 1997;57:1731–1734.PubMedGoogle Scholar
  11. 11.
    Maitra A, Adsay NV, Argani P, Iacobuzio-Donahue C, De Marzo A, Cameron JL, Yeo CJ, Hruban RH: Multicomponent analysis of the pancreatic adenocarcinoma progression model using a pancreatic intraepithelial neoplasia tissue microarray. Mod Pathol 2003;16:902–912.CrossRefPubMedGoogle Scholar
  12. 12.
    Yokoyama M, Yamanaka Y, Friess H, Buchler M, Korc M: p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness. Anticancer Res 1994;14:2477–2483.PubMedGoogle Scholar
  13. 13.
    Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE: DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996;271:350–353.CrossRefPubMedGoogle Scholar
  14. 14.
    Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, et al.: Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008;321:1801–1806.CrossRefPubMedGoogle Scholar
  15. 15.
    Maitra A, Fukushima N, Takaori K, Hruban RH: Precursors to invasive pancreatic cancer. Adv Anat Pathol 2005;12:81–91.CrossRefPubMedGoogle Scholar
  16. 16.
    Pour P, Kruger FW, Althoff J, Cardesa A, Mohr U: Effect of beta-oxidized nitrosamines on syrian hamsters. III. 2,2′-Dihydroxydi-n-propylnitrosamine. J Natl Cancer Inst 1975b;54:141–146.PubMedGoogle Scholar
  17. 17.
    Pour P, Althoff J, Kruger F, Schmahl D, Mohr U: Induction of pancreatic neoplasms by 2,2′-dioxopropyl-N-propylnitrosamine. Cancer Lett 1975a;1:3–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Levitt M, Harris C, Squire R, Wenk M, Mollelo C, Springer S: Experimental pancreatic carcinogenesis. II. Lifetime carcinogenesis studies in the outbred Syrian golden hamster with N-nitroso-bis(2-hydroxypropyl)amine. J Natl Cancer Inst 1978;60:701–705.PubMedGoogle Scholar
  19. 19.
    Pour P, Althoff J, Gingell R, Kupper R, Kruger F, Mohr U: N-nitroso-bis(2-acetoxypropyl)amine as a further pancreatic carcinogen in Syrian golden hamsters. Cancer Res 1976;36:2877–2884.PubMedGoogle Scholar
  20. 20.
    Pour P, Althoff J, Kruger FW, Mohr U: A potent pancreatic carcinogen in Syrian hamsters: N-nitrosobis(2-oxopropyl)amine. J Natl Cancer Inst 1977;58:1449–1453.PubMedGoogle Scholar
  21. 21.
    Dissin J, Mills LR, Mains DL, Black O, Jr., Webster PD, 3rd: Experimental induction of pancreatic adenocarcinoma in rats. J Natl Cancer Inst 1975;55:857–864.PubMedGoogle Scholar
  22. 22.
    Longnecker DS, Curphey TJ: Adenocarcinoma of the pancreas in azaserine-treated rats. Cancer Res 1975;35:2249–2258.PubMedGoogle Scholar
  23. 23.
    Osvaldt AB, Wendt LR, Bersch VP, Backes AN, de Cassia ASR, Edelweiss MI, Rohde L: Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice. Surgery 2006;140:803–809.CrossRefPubMedGoogle Scholar
  24. 24.
    Levitt MH, Harris CC, Squire R, Springer S, Wenk M, Mollelo C, Thomas D, Kingsbury E, Newkirk C: Experimental pancreatic carcinogenesis. I. Morphogenesis of pancreatic adenocarcinoma in the Syrian golden hamster induced by N-nitroso-bis(2-hydroxypropyl)amine. Am J Pathol 1977;88:5–28.PubMedGoogle Scholar
  25. 25.
    Pour P, Althoff J: The effect of N-nitrosobis(2-oxopropyl)amine after oral administration to hamsters. Cancer Lett 1977;2:323–326.CrossRefPubMedGoogle Scholar
  26. 26.
    Pour PM: Experimental pancreatic cancer. Am J Surg Pathol 1989;13:Suppl 1, 96–103.PubMedGoogle Scholar
  27. 27.
    Chang KW, Laconi S, Mangold KA, Hubchak S, Scarpelli DG: Multiple genetic alterations in hamster pancreatic ductal adenocarcinomas. Cancer Res 1995;55:2560–2568.PubMedGoogle Scholar
  28. 28.
    Hotz HG, Hines OJ, Foitzik T, Reber HA: Animal models of exocrine pancreatic cancer. Int J Colorectal Dis 2000;15:136–143.CrossRefPubMedGoogle Scholar
  29. 29.
    Rao MS: Animal models of exocrine pancreatic carcinogenesis. Cancer Metastasis Rev 1987;6:665–676.CrossRefPubMedGoogle Scholar
  30. 30.
    Pour P, Salmasi S, Runge R, Gingell R, Wallcave L, Nagel D, Stepan K: Carcinogenicity of N-nitrosobis(2-hydroxypropyl)amine and N-nitrosobis(2-oxopropyl)amine in MRC rats. J Natl Cancer Inst 1979;63:181–190.PubMedGoogle Scholar
  31. 31.
    Bockman DE, Black O, Jr., Mills LR, Mainz DL, Webster PD, 3rd: Fine structure of pancreatic adenocarcinoma induced in rats by 7,12-dimethylbenz(a)anthracene. J Natl Cancer Inst 1976;57:931–936.PubMedGoogle Scholar
  32. 32.
    Longnecker DS, Roebuck BD, Yager JD, Jr., Lilja HS, Siegmund B: Pancreatic carcinoma in azaserine-treated rats: induction, classification and dietary modulation of incidence. Cancer 1981;47:1562–1572.CrossRefPubMedGoogle Scholar
  33. 33.
    Schaeffer BK, Zurlo J, Longnecker DS: Activation of c-Ki-ras not detectable in adenomas or adenocarcinomas arising in rat pancreas. Mol Carcinog 1990;3:165–170.CrossRefPubMedGoogle Scholar
  34. 34.
    Wendt LR, Osvaldt AB, Bersch VP, Schumacher Rde C, Edelweiss MI, Rohde L: Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice: effects of alcohol and caffeine. Acta cirurgica brasileira/Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia 2007;22:202–209.PubMedGoogle Scholar
  35. 35.
    Bersch VP, Osvaldt AB, Edelweiss MI, Schumacher RD, Wendt LR, Abreu LP, Blom CB, Abreu GP, Costa L, Piccinini P, Rohde L: Effect of Nicotine and Cigarette Smoke on an Experimental Model of Intraepithelial Lesions and Pancreatic Adenocarcinoma Induced by 7,12-Dimethylbenzanthracene in Mice. Pancreas.2008;38(1):65–70.CrossRefGoogle Scholar
  36. 36.
    Erill N, Cuatrecasas M, Sancho FJ, Farre A, Pour PM, Lluis F, Capella G: K-ras and p53 mutations in hamster pancreatic ductal adenocarcinomas and cell lines. Am J Pathol 1996;149:1333–1339.PubMedGoogle Scholar
  37. 37.
    Egami H, Tomioka T, Tempero M, Kay D, Pour PM: Development of intrapancreatic transplantable model of pancreatic duct adenocarcinoma in Syrian golden hamsters. Am J Pathol 1991;138:557–561.PubMedGoogle Scholar
  38. 38.
    Hotz HG, Reber HA, Hotz B, Foitzik T, Buhr HJ, Cortina G, Hines OJ: An improved clinical model of orthotopic pancreatic cancer in immunocompetent Lewis rats. Pancreas 2001;22:113–121.CrossRefPubMedGoogle Scholar
  39. 39.
    Tan MH, Chu TM: Characterization of the tumorigenic and metastatic properties of a human pancreatic tumor cell line (AsPC-1) implanted orthotopically into nude mice. Tumour Biol 1985;6:89–98.PubMedGoogle Scholar
  40. 40.
    Mohammad RM, Al-Katib A, Pettit GR, Vaitkevicius VK, Joshi U, Adsay V, Majumdar AP, Sarkar FH: An orthotopic model of human pancreatic cancer in severe combined immunodeficient mice: potential application for preclinical studies. Clin Cancer Res 1998;4:887–894.PubMedGoogle Scholar
  41. 41.
    Marincola FM, Drucker BJ, Siao DY, Hough KL, Holder WD, Jr.: The nude mouse as a model for the study of human pancreatic cancer. J Surg Res 1989;47:520–529.CrossRefPubMedGoogle Scholar
  42. 42.
    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 USA 1992;89:5645–5649.CrossRefPubMedGoogle Scholar
  43. 43.
    Swift GH, Hammer RE, MacDonald RJ, Brinster RL: Tissue-specific expression of the rat pancreatic elastase I gene in transgenic mice. Cell 1984;38:639–646.CrossRefPubMedGoogle Scholar
  44. 44.
    Ornitz DM, Palmiter RD, Hammer RE, Brinster RL, Swift GH, MacDonald RJ: Specific expression of an elastase-human growth hormone fusion gene in pancreatic acinar cells of transgenic mice. Nature 1985;313:600–602.CrossRefPubMedGoogle Scholar
  45. 45.
    Ornitz DM, Hammer RE, Messing A, Palmiter RD, Brinster RL: Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science 1987;238:188–193.CrossRefPubMedGoogle Scholar
  46. 46.
    Quaife CJ, Pinkert CA, Ornitz DM, Palmiter RD, Brinster RL: Pancreatic neoplasia induced by ras expression in acinar cells of transgenic mice. Cell 1987;48:1023–1034.CrossRefPubMedGoogle Scholar
  47. 47.
    Sandgren EP, Quaife CJ, Paulovich AG, Palmiter RD, Brinster RL: Pancreatic tumor pathogenesis reflects the causative genetic lesion. Proc Natl Acad Sci USA 1991;88:93–97.CrossRefPubMedGoogle Scholar
  48. 48.
    Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC: Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 1990;61:1121–1135.CrossRefPubMedGoogle Scholar
  49. 49.
    Schmid RM, Kloppel G, Adler G, Wagner M: Acinar-ductal-carcinoma sequence in transforming growth factor-alpha transgenic mice. Ann NY Acad Sci 1999;880:219–230.CrossRefPubMedGoogle Scholar
  50. 50.
    Grippo PJ, Nowlin PS, Demeure MJ, Longnecker DS, Sandgren EP: Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice. Cancer Res 2003;63:2016–2019.PubMedGoogle Scholar
  51. 51.
    Brembeck FH, Schreiber FS, Deramaudt TB, Craig L, Rhoades B, Swain G, Grippo P, Stoffers DA, Silberg DG, Rustgi AK: The mutant K-ras oncogene causes pancreatic periductal lymphocytic infiltration and gastric mucous neck cell hyperplasia in transgenic mice. Cancer Res 2003;63:2005–2009.PubMedGoogle Scholar
  52. 52.
    Kim SK, MacDonald RJ: Signaling and transcriptional control of pancreatic organogenesis. Curr Opin Genet Dev 2002;12:540–547.CrossRefPubMedGoogle Scholar
  53. 53.
    Ahlgren U, Jonsson J, Edlund H: The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice. Development 1996;122:1409–1416.PubMedGoogle Scholar
  54. 54.
    Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CV: The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 2002;32:128–134.CrossRefPubMedGoogle Scholar
  55. 55.
    Offield MF, Jetton TL, Labosky PA, Ray M, Stein RW, Magnuson MA, Hogan BL, Wright CV: PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 1996;122:983–995.PubMedGoogle Scholar
  56. 56.
    Krapp A, Knofler M, Ledermann B, Burki K, Berney C, Zoerkler N, Hagenbuchle O, Wellauer PK: 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;12:3752–3763.CrossRefPubMedGoogle Scholar
  57. 57.
    Lakso M, Sauer B, Mosinger B, Jr., Lee EJ, Manning RW, Yu SH, Mulder KL, Westphal H: Targeted oncogene activation by site-specific recombination in transgenic mice. Proc Natl Acad Sci USA 1992;89:6232–6236.CrossRefPubMedGoogle Scholar
  58. 58.
    Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T, Tuveson DA: Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 2001;15:3243–3248.CrossRefPubMedGoogle Scholar
  59. 59.
    Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, Ross S, Conrads TP, Veenstra TD, Hitt BA, et al.: Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 2003;4:437–450.CrossRefPubMedGoogle Scholar
  60. 60.
    Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J, Redston MS, DePinho RA: Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 2003;17:3112–3126.CrossRefPubMedGoogle Scholar
  61. 61.
    Hustinx SR, Leoni LM, Yeo CJ, Brown PN, Goggins M, Kern SE, Hruban RH, Maitra A: Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol 2005;18:959–963.CrossRefPubMedGoogle Scholar
  62. 62.
    Bardeesy N, Aguirre AJ, Chu GC, Cheng KH, Lopez LV, Hezel AF, Feng B, Brennan C, Weissleder R, Mahmood U, et al.: Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc Natl Acad Sci USA 2006a 103:5947–5952.CrossRefPubMedGoogle Scholar
  63. 63.
    Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P: The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 2002;19:607–614.CrossRefPubMedGoogle Scholar
  64. 64.
    Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, Rustgi AK, Chang S, Tuveson DA: Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005;7:469–483.CrossRefPubMedGoogle Scholar
  65. 65.
    Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, Dubus P, Sandgren EP, Barbacid M: Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 2007;11:291–302.CrossRefPubMedGoogle Scholar
  66. 66.
    Malka D, Hammel P, Maire F, Rufat P, Madeira I, Pessione F, Levy P, Ruszniewski P: Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut 2002;51:849–852.CrossRefPubMedGoogle Scholar
  67. 67.
    Hansel DE, Kern SE, Hruban RH: Molecular pathogenesis of pancreatic cancer. Annu Rev Genomics Hum Genet 2003;4:237–256.CrossRefPubMedGoogle Scholar
  68. 68.
    Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, et al.: Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science (New York, NY 1998;280:1086–1088.CrossRefPubMedGoogle Scholar
  69. 69.
    Bierie B, Moses HL: Tumour microenvironment: TGFbeta: The molecular Jekyll and Hyde of cancer. Nat Rev 2006;6:506–520.Google Scholar
  70. 70.
    Takaku K, Miyoshi H, Matsunaga A, Oshima M, Sasaki N, Taketo MM: Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice. Cancer Res 1999;59:6113–6117.PubMedGoogle Scholar
  71. 71.
    Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, Hezel AF, Horner J, Lauwers GY, Hanahan D, DePinho RA: Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev 2006b;20:3130–3146.CrossRefPubMedGoogle Scholar
  72. 72.
    Iacobuzio-Donahue CA, Klimstra DS, Adsay NV, Wilentz RE, Argani P, Sohn TA, Yeo CJ, Cameron JL, Kern SE, Hruban RH: Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: comparison with conventional ductal adenocarcinomas. Am J Pathol 2000;157:755–761.PubMedGoogle Scholar
  73. 73.
    Izeradjene K, Combs C, Best M, Gopinathan A, Wagner A, Grady WM, Deng CX, Hruban RH, Adsay NV, Tuveson DA, Hingorani SR: Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell 2007;11:229–243.CrossRefPubMedGoogle Scholar
  74. 74.
    Zhang Z, Wang Y, Vikis HG, Johnson L, Liu G, Li J, Anderson MW, Sills RC, Hong HL, Devereux TR, et al.: Wildtype Kras2 can inhibit lung carcinogenesis in mice. Nat Genet 2001;29:25–33.CrossRefPubMedGoogle Scholar
  75. 75.
    van Heek NT, Meeker AK, Kern SE, Yeo CJ, Lillemoe KD, Cameron JL, Offerhaus GJ, Hicks JL, Wilentz RE, Goggins MG, et al.: Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am J Pathol 2002;161:1541–1547.PubMedGoogle Scholar
  76. 76.
    Leach SD: Epithelial differentiation in pancreatic development and neoplasia: new niches for nestin and Notch. J Clin Gastroenterol 2005;39:S78–S82.CrossRefPubMedGoogle Scholar
  77. 77.
    Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM: Identification of pancreatic cancer stem cells. Cancer Res 2007;67:1030–1037.CrossRefPubMedGoogle Scholar
  78. 78.
    O’Brien CA, Pollett A, Gallinger S, Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106–110.CrossRefPubMedGoogle Scholar
  79. 79.
    Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature 2007;445:111–115.CrossRefPubMedGoogle Scholar
  80. 80.
    Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C: Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007;1:313–323.CrossRefPubMedGoogle Scholar
  81. 81.
    Hess V, Glimelius B, Grawe P, Dietrich D, Bodoky G, Ruhstaller T, Bajetta E, Saletti P, Figer A, Scheithauer W, Herrmann R: CA 19–9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. lancet Oncol 2008;9:132–138.CrossRefPubMedGoogle Scholar
  82. 82.
    Faca VM, Song KS, Wang H, Zhang Q, Krasnoselsky AL, Newcomb LF, Plentz RR, Gurumurthy S, Redston MS, Pitteri SJ, et al.: A mouse to human search for plasma proteome changes associated with pancreatic tumor development. PLoS Med 2008;5:e123.CrossRefPubMedGoogle Scholar
  83. 83.
    Collier LS, Carlson CM, Ravimohan S, Dupuy AJ, Largaespada DA: Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature 2005;436:272–276.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michelle Lockley
    • 1
  • David Tuveson
    • 2
  1. 1.University of CambridgeCambridgeLondon
  2. 2.Cancer Research UKCambridgeUK

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