Skip to main content

Advancements in Modeling Colorectal Cancer in Rodents

Abstract

Colorectal cancer (CRC) has become a large burden on the health care system with 700,000 people dying from this disease annually in the world. Rodent cancer models, especially the mouse models, play critical roles in the understanding of CRC etiology and the development of CRC therapies. This review is focused on reporting the significant progress that has been made in CRC studies using transplant models and forward genetics mouse models. Rat CRC models are also described as they were usually skipped in other related reviews. We also try to discuss what needs to be improved in rodent model studies to better serve as the CRC research tools and preclinical models for patient care and treatments.

This is a preview of subscription content, access via your institution.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi:10.3322/caac.21262.

    PubMed  Article  Google Scholar 

  2. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010–2020. J Natl Cancer Inst. 2011;103(2):117–28. doi:10.1093/jnci/djq495.

    PubMed  PubMed Central  Article  Google Scholar 

  3. Nandan MO, Yang VW. Genetic and chemical models of colorectal cancer in mice. Current Colorectal Cancer Reports. 2010;6(2):51–9. doi:10.1007/s11888-010-0046-1. This previous review paper published here in this joural provides detailed description of classical GEM models of CRC.

    PubMed  PubMed Central  Article  Google Scholar 

  4. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science (New York, NY). 1997;275(5307):1787-90.

  5. Moser AR, Pitot HC, Dove WF. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science (New York, NY). 1990;247(4940):322-4.

  6. Oshima M, Oshima H, Kitagawa K, Kobayashi M, Itakura C, Taketo M. Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene. Proc Natl Acad Sci U S A. 1995;92(10):4482–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. Fodde R, Edelmann W, Yang K, van Leeuwen C, Carlson C, Renault B, et al. A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc Natl Acad Sci U S A. 1994;91(19):8969–73.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. Colnot S, Niwa-Kawakita M, Hamard G, Godard C, Le Plenier S, Houbron C, et al. Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers. Lab Investig. 2004;84(12):1619–30. doi:10.1038/labinvest.3700180.

    CAS  PubMed  Article  Google Scholar 

  9. Pollard P, Deheragoda M, Segditsas S, Lewis A, Rowan A, Howarth K, et al. The Apc 1322T mouse develops severe polyposis associated with submaximal nuclear beta-catenin expression. Gastroenterology. 2009;136(7):2204–13. doi:10.1053/j.gastro.2009.02.058. e1-13.

    CAS  PubMed  Article  Google Scholar 

  10. Gaspar C, Franken P, Molenaar L, Breukel C, van der Valk M, Smits R, et al. A targeted constitutive mutation in the APC tumor suppressor gene underlies mammary but not intestinal tumorigenesis. PLoS Genet. 2009;5(7):e1000547. doi:10.1371/journal.pgen.1000547.

    PubMed  PubMed Central  Article  Google Scholar 

  11. Shibata H, Toyama K, Shioya H, Ito M, Hirota M, Hasegawa S et al. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science (New York, NY). 1997;278(5335):120-3.

  12. Powell AE, Wang Y, Li Y, Poulin EJ, Means AL, Washington MK, et al. The Pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell. 2012;149:146–58. This paper reported a new Cre mouse strain that leads to the development of both small intestinal tumors and colon tumors.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. Powell AE, Vlacich G, Zhao ZY, McKinley ET, Washington MK, Manning HC, et al. Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis. Am J Physiol Gastrointest Liver Physiol. 2014;307(1):G16–23. doi:10.1152/ajpgi.00358.2013.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–67. Proposed the widely accepted sequencial genetic model of CRC.

    CAS  PubMed  Article  Google Scholar 

  15. TCGA. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–7. doi:10.1038/nature11252.

    Article  Google Scholar 

  16. Massague J. TGFbeta signalling in context. Nat Rev Mol Cell Biol. 2012;13(10):616–30. doi:10.1038/nrm3434.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Hamelin R, Laurent-Puig P, Olschwang S, Jego N, Asselain B, Remvikos Y, et al. Association of p53 mutations with short survival in colorectal cancer. Gastroenterology. 1994;106(1):42–8.

    CAS  PubMed  Article  Google Scholar 

  18. Janssen KP, el-Marjou F, Pinto D, Sastre X, Rouillard D, Fouquet C. Targeted expression of oncogenic K-ras in intestinal epithelium causes spontaneous tumorigenesis in mice. Gastroenterology. 2002;123(2):492–504.

    CAS  PubMed  Article  Google Scholar 

  19. Johnson L, Mercer K, Greenbaum D, Bronson RT, Crowley D, Tuveson DA, et al. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature. 2001;410(6832):1111–6. doi:10.1038/35074129.

    CAS  PubMed  Article  Google Scholar 

  20. Zhu Y, Richardson JA, Parada LF, Graff JM. Smad3 mutant mice develop metastatic colorectal cancer. Cell. 1998;94(6):703–14.

    CAS  PubMed  Article  Google Scholar 

  21. 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(24):6113–7.

    CAS  PubMed  Google Scholar 

  22. Engle SJ, Hoying JB, Boivin GP, Ormsby I, Gartside PS, Doetschman T. Transforming growth factor beta1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis. Cancer Res. 1999;59(14):3379–86.

    CAS  PubMed  Google Scholar 

  23. Trobridge P, Knoblaugh S, Washington MK, Munoz NM, Tsuchiya KD, Rojas A, et al. TGF-beta receptor inactivation and mutant Kras induce intestinal neoplasms in mice via a beta-catenin-independent pathway. Gastroenterology. 2009;136(5):1680–8. doi:10.1053/j.gastro.2009.01.066. e7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Muller PA, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, et al. Mutant p53 drives invasion by promoting integrin recycling. Cell. 2009;139(7):1327–41. doi:10.1016/j.cell.2009.11.026.

    PubMed  Article  Google Scholar 

  25. Kucherlapati MH, Lee K, Nguyen AA, Clark AB, Hou Jr H, Rosulek A, et al. An Msh2 conditional knockout mouse for studying intestinal cancer and testing anticancer agents. Gastroenterology. 2010;138(3):993–1002. doi:10.1053/j.gastro.2009.11.009. e1.

    PubMed  Article  Google Scholar 

  26. Edelmann W, Umar A, Yang K, Heyer J, Kucherlapati M, Lia M, et al. The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression. Cancer Res. 2000;60(4):803–7.

    CAS  PubMed  Google Scholar 

  27. Edelmann W, Yang K, Kuraguchi M, Heyer J, Lia M, Kneitz B, et al. Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Res. 1999;59(6):1301–7.

    CAS  PubMed  Google Scholar 

  28. Chen PC, Dudley S, Hagen W, Dizon D, Paxton L, Reichow D, et al. Contributions by MutL homologues Mlh3 and Pms2 to DNA mismatch repair and tumor suppression in the mouse. Cancer Res. 2005;65(19):8662–70. doi:10.1158/0008-5472.can-05-0742.

    CAS  PubMed  Article  Google Scholar 

  29. Copeland NG, Jenkins NA. Harnessing transposons for cancer gene discovery. Nat Rev Cancer. 2010;10(10):696–706. doi:10.1038/nrc2916.

    CAS  PubMed  Article  Google Scholar 

  30. Starr TK, Allaei R, Silverstein KAT, Staggs RA, Sarver AL, Bergemann TL, et al. A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science. 2009;323(5922):1747–50. This was the first published SB transposon mutagenesis study for CRC.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. March HN, Rust AG, Wright NA, Hoeve J, Jd R, Eldridge M, et al. Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis. Nat Genet. 2011;43:1202–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Starr TK, Scott PM, Marsh BM, Zhao L, Than BLN, O’Sullivan MG, et al. A Sleeping Beauty transposon-mediated screen identifies murine susceptibility genes for adenomatous polyposis coli (Apc)-dependent intestinal tumorigenesis. Proc Natl Acad Sci U S A. 2011;108(14):5765–70.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. Kale VP, Amin SG, Pandey MK. Targeting ion channels for cancer therapy by repurposing the approved drugs. Biochim Biophys Acta. 2015;1848(10 Pt B):2747-55. doi:10.1016/j.bbamem.2015.03.034.

  34. Takeda H, Wei Z, Koso H, Rust AG, Yew CC, Mann MB, et al. Transposon mutagenesis identifies genes and evolutionary forces driving gastrointestinal tract tumor progression. Nat Genet. 2015;47(2):142–50. doi:10.1038/ng.3175. Most recent SB transposon screens for CRC with different genetic backgrounds. Both initiation and progression of intestinal tumors were covered in these screens.

    CAS  PubMed  Article  Google Scholar 

  35. Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res. 2003;9(11):4227–39.

    PubMed  Google Scholar 

  36. Croy BA, Linder KE, Yager JA. Primer for non-immunologists on immune-deficient mice and their applications in research. Comp Med. 2001;51(4):300–13.

    CAS  PubMed  Google Scholar 

  37. Choi SY, Lin D, Gout PW, Collins CC, Xu Y, Wang Y. Lessons from patient-derived xenografts for better in vitro modeling of human cancer. Adv Drug Deliv Rev. 2014;79-80:222-37. doi:10.1016/j.addr.2014.09.009.

  38. Rosfjord E, Lucas J, Li G, Gerber HP. Advances in patient-derived tumor xenografts: from target identification to predicting clinical response rates in oncology. Biochem Pharmacol. 2014;91(2):135–43. doi:10.1016/j.bcp.2014.06.008.

    CAS  PubMed  Article  Google Scholar 

  39. Aparicio S, Hidalgo M, Kung AL. Examining the utility of patient-derived xenograft mouse models. Nat Rev Cancer. 2015;15(5):311–6. doi:10.1038/nrc3944. Review the generation of PDX mouse model and its applications as pre-clinical drug models in therapeutic study.

    CAS  PubMed  Article  Google Scholar 

  40. Burgenske DM, Monsma DJ, Dylewski D, Scott SB, Sayfie AD, Kim DG, et al. Establishment of genetically diverse patient-derived xenografts of colorectal cancer. Am J Cancer Res. 2014;4(6):824–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Chen HJ, Edwards R, Tucci S, Bu P, Milsom J, Lee S, et al. Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis. J Clin Invest. 2012;122(9):3184–96. doi:10.1172/JCI62110.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. Julien S, Merino-Trigo A, Lacroix L, Pocard M, Goere D, Mariani P, et al. Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin Cancer Res. 2012;18(19):5314–28. doi:10.1158/1078-0432.CCR-12-0372.

    CAS  PubMed  Article  Google Scholar 

  43. 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(9):873–7.

    PubMed  PubMed Central  Google Scholar 

  44. Siolas D, Hannon GJ. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 2013;73(17):5315–9. doi:10.1158/0008-5472.CAN-13-1069.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. Uronis JM, Osada T, McCall S, Yang XY, Mantyh C, Morse MA, et al. Histological and molecular evaluation of patient-derived colorectal cancer explants. PLoS One. 2012;7(6):e38422. doi:10.1371/journal.pone.0038422.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. Williams SA, Anderson WC, Santaguida MT, Dylla SJ. Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century. Lab Investig. 2013;93(9):970–82. doi:10.1038/labinvest.2013.92.

    PubMed  Article  Google Scholar 

  47. Chen HJ, Sun J, Huang Z, Hou Jr H, Arcilla M, Rakhilin N, et al. Comprehensive models of human primary and metastatic colorectal tumors in immunodeficient and immunocompetent mice by chemokine targeting. Nat Biotechnol. 2015;33(6):656–60. doi:10.1038/nbt.3239. Developed a new method to engineering surgery-free orthotopic CRC models and controllable metastatic switches.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. Morelli MP, Calvo E, Ordonez E, Wick MJ, Viqueira BR, Lopez-Casas PP, et al. Prioritizing phase I treatment options through preclinical testing on personalized tumorgraft. J Clin Oncol. 2012;30(4):e45–8. doi:10.1200/JCO.2011.36.9678.

    CAS  PubMed  Article  Google Scholar 

  49. Ootani A, Li X, Sangiorgi E, Ho QT, Ueno H, Toda S, et al. Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med. 2009;15(6):701–6. doi:10.1038/nm.1951.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Nat Med. 2012;18(4):618–23. doi:10.1038/nm.2695.

    CAS  PubMed  Article  Google Scholar 

  51. Jung P, Sato T, Merlos-Suarez A, Barriga FM, Iglesias M, Rossell D, et al. Isolation and in vitro expansion of human colonic stem cells. Nat Med. 2011;17(10):1225–7. doi:10.1038/nm.2470.

    CAS  PubMed  Article  Google Scholar 

  52. Miyoshi H, Stappenbeck TS. In vitro expansion and genetic modification of gastrointestinal stem cells in spheroid culture. Nat Protoc. 2013;8(12):2471–82. doi:10.1038/nprot.2013.153.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009;459(7244):262–5. doi:10.1038/nature07935.

    CAS  PubMed  Article  Google Scholar 

  54. Benton G, Arnaoutova I, George J, Kleinman HK, Koblinski J. Matrigel: From discovery and ECM mimicry to assays and models for cancer research. Adv Drug Deliv Rev. 2014;79-80:3-18. doi:10.1016/j.addr.2014.06.005.

  55. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449(7165):1003–7. doi:10.1038/nature06196.

    CAS  PubMed  Article  Google Scholar 

  56. Drost J, van Jaarsveld RH, Ponsioen B, Zimberlin C, van Boxtel R, Buijs A, et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature. 2015;521(7550):43–7. doi:10.1038/nature14415.

    CAS  PubMed  Article  Google Scholar 

  57. Matano M, Date S, Shimokawa M, Takano A, Fujii M, Ohta Y, et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med. 2015;21(3):256–62. doi:10.1038/nm.3802. Modeling CRC initiation and progression using organoids with new genetic editing tool.

    CAS  PubMed  Google Scholar 

  58. Li X, Nadauld L, Ootani A, Corney DC, Pai RK, Gevaert O, et al. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat Med. 2014;20(7):769–77. doi:10.1038/nm.3585.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F, Pronk A, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 2015;161(4):933–45. doi:10.1016/j.cell.2015.03.053.

    PubMed  Article  Google Scholar 

  60. Merlos-Suarez A, Barriga FM, Jung P, Iglesias M, Cespedes MV, Rossell D, et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. 2011;8(5):511–24. doi:10.1016/j.stem.2011.02.020.

    CAS  PubMed  Article  Google Scholar 

  61. Walters S, Maringe C, Butler J, Brierley JD, Rachet B, Coleman MP. Comparability of stage data in cancer registries in six countries: lessons from the International Cancer Benchmarking Partnership. Int J Cancer. 2013;132(3):676–85. doi:10.1002/ijc.27651.

    CAS  PubMed  Article  Google Scholar 

  62. de Jong GM, Aarts F, Hendriks T, Boerman OC, Bleichrodt RP. Animal models for liver metastases of colorectal cancer: research review of preclinical studies in rodents. J Surg Res. 2009;154(1):167–76. doi:10.1016/j.jss.2008.03.038.

    PubMed  Article  Google Scholar 

  63. Kobaek-Larsen M, Thorup I, Diederichsen A, Fenger C, Hoitinga MR. Review of colorectal cancer and its metastases in rodent models: comparative aspects with those in humans. Comp Med. 2000;50(1):16–26.

    CAS  PubMed  Google Scholar 

  64. Cespedes MV, Espina C, Garcia-Cabezas MA, Trias M, Boluda A, del Pulgar MT G, et al. Orthotopic microinjection of human colon cancer cells in nude mice induces tumor foci in all clinically relevant metastatic sites. Am J Pathol. 2007;170(3):1077–85. doi:10.2353/ajpath.2007.060773.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. Talmadge JE, Singh RK, Fidler IJ, Raz A. Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol. 2007;170(3):793–804. doi:10.2353/ajpath.2007.060929.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. DiMasi JA, Reichert JM, Feldman L, Malins A. Clinical approval success rates for investigational cancer drugs. Clin Pharmacol Ther. 2013;94(3):329–35. doi:10.1038/clpt.2013.117.

    CAS  PubMed  Article  Google Scholar 

  67. Rubio-Viqueira B, Hidalgo M. Direct in vivo xenograft tumor model for predicting chemotherapeutic drug response in cancer patients. Clin Pharmacol Ther. 2009;85(2):217–21. doi:10.1038/clpt.2008.200.

    CAS  PubMed  Article  Google Scholar 

  68. Sausville EA, Burger AM. Contributions of human tumor xenografts to anticancer drug development. Cancer Res. 2006;66(7):3351–4. doi:10.1158/0008-5472.CAN-05-3627. discussion 4.

    CAS  PubMed  Article  Google Scholar 

  69. Bretagnol F, Maggiori L, Zappa M, Sibert A, Vilgrain V, Panis Y. Selective portal vein embolization and colorectal liver metastases in rat: a new experimental model for tumor growth study. J Surg Res. 2011;171(2):669–74. doi:10.1016/j.jss.2010.03.047.

    PubMed  Article  Google Scholar 

  70. Kuo TH, Kubota T, Watanabe M, Furukawa T, Teramoto T, Ishibiki K, et al. Liver colonization competence governs colon cancer metastasis. Proc Natl Acad Sci U S A. 1995;92(26):12085–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. Bouvet M, Tsuji K, Yang M, Jiang P, Moossa AR, Hoffman RM. In vivo color-coded imaging of the interaction of colon cancer cells and splenocytes in the formation of liver metastases. Cancer Res. 2006;66(23):11293–7. doi:10.1158/0008-5472.CAN-06-2662.

    CAS  PubMed  Article  Google Scholar 

  72. Donigan M, Loh BD, Norcross LS, Li S, Williamson PR, DeJesus S, et al. A metastatic colon cancer model using nonoperative transanal rectal injection. Surg Endosc. 2010;24(3):642–7. doi:10.1007/s00464-009-0650-9.

    PubMed  Article  Google Scholar 

  73. Alamo P, Gallardo A, Di Nicolantonio F, Pavon MA, Casanova I, Trias M, et al. Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model. FASEB J. 2015;29(2):464–76. doi:10.1096/fj.14-262303.

    CAS  PubMed  Article  Google Scholar 

  74. Morimoto-Tomita M, Ohashi Y, Matsubara A, Tsuiji M, Irimura T. Mouse colon carcinoma cells established for high incidence of experimental hepatic metastasis exhibit accelerated and anchorage-independent growth. Clin Exp Metastasis. 2005;22(6):513–21. doi:10.1007/s10585-005-3585-0.

    PubMed  Article  Google Scholar 

  75. Guo X, Brenner M, Zhang X, Laragione T, Tai S, Li Y, et al. Whole-genome sequences of DA and F344 rats with different susceptibilities to arthritis, autoimmunity, inflammation and cancer. Genetics. 2013;194(4):1017–28. doi:10.1534/genetics.113.153049.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. Worthey EA, Stoddard AJ, Jacob HJ. Sequencing of the rat genome and databases. Methods Mol. Biol. (Clifton, NJ). 2010;597:33-53. doi:10.1007/978-1-60327-389-3_3.

  77. Amos-Landgraf JM, Kwong LN, Kendziorski CM, Reichelderfer M, Torrealba J, Weichert J, et al. A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Proc Natl Acad Sci U S A. 2007;104(10):4036–41. doi:10.1073/pnas.0611690104.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. Yoshimi K, Tanaka T, Takizawa A, Kato M, Hirabayashi M, Mashimo T, et al. Enhanced colitis-associated colon carcinogenesis in a novel Apc mutant rat. Cancer Sci. 2009;100(11):2022–7. doi:10.1111/j.1349-7006.2009.01287.x.

    CAS  PubMed  Article  Google Scholar 

  79. Olive D, Savoldo B, Pastorino F, Castriconi R. Immunotherapy in the treatment of human solid tumors: basic and translational aspects. J Immunol Res. 2016;2016:7853028. doi:10.1155/2016/7853028.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  80. Link JT, Overman MJ. Immunotherapy progress in mismatch repair-deficient colorectal cancer and future therapeutic challenges. Cancer J (Sudbury, Mass). 2016;22(3):190-5. doi:10.1097/ppo.0000000000000196.

  81. Graham DM, Coyle VM, Kennedy RD, Wilson RH. Molecular subtypes and personalized therapy in metastatic colorectal cancer. Current Colorectal Cancer Reports. 2016;12:141–50. doi:10.1007/s11888-016-0312-y.

    PubMed  PubMed Central  Article  Google Scholar 

  82. Hunter KW. Mouse models of cancer: does the strain matter? Nat Rev Cancer. 2012;12(2):144–9. doi:10.1038/nrc3206. Discussed how mouse strains may affect the appropriate explanations of experimental results.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by NCI-PSOC Young Investigator trans-network grant (to H.J.C and Z.W.) and Arnold O. Beckman Postdoctoral fellowship (to H.J.C).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Huanhuan Joyce Chen or Zhubo Wei.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Molecular Biology

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chen, H.J., Zheng, Y. & Wei, Z. Advancements in Modeling Colorectal Cancer in Rodents. Curr Colorectal Cancer Rep 12, 274–280 (2016). https://doi.org/10.1007/s11888-016-0334-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-016-0334-5

Keywords

  • Colorectal cancer
  • GEM models
  • Transposon insertional mutagenesis
  • Patient-derived xenograft
  • Organoid xenograft
  • Orthotopic xenograft
  • Metastatic models
  • Rat CRC models