Using genetically engineered mouse models to validate candidate cancer genes and test new therapeutic approaches

Current Opinion in Genetics and Development

Volumn 22, Issue 1, 2012, Pages 21-27

  van Miltenburg, Martine H ^a   Jonkers, Jos ^a  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; BRCA1 PROTEIN; BRCA2 PROTEIN; ESTROGEN RECEPTOR BETA; GLYCOPROTEIN P; MITOGEN ACTIVATED PROTEIN KINASE 1; MYC PROTEIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN P53; RAF PROTEIN; RAS PROTEIN; TRANSACTIVATOR PROTEIN;

ANGIOGENESIS; CANCER GENETICS; CANCER INVASION; CANCER RESEARCH; EMBRYONIC STEM CELL; EXON; GENE ACTIVATION; GENE DELETION; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE MUTATION; GENOTYPE; INFLAMMATION; LOXP SITE; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVERTANT; REVIEW; TRANSGENIC MOUSE; TUMOR GENE;

ANIMALS; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, NEOPLASM; HUMANS; MICE; MICE, TRANSGENIC; NEOPLASMS;

EID: 84858439380     PISSN: 0959437X     EISSN: 18790380     Source Type: Journal    
DOI: 10.1016/j.gde.2012.01.004     Document Type: Review

References (56)

1. Jonkers J., Berns A. Conditional mouse models of sporadic cancer. Nat Rev Cancer 2002, 2:251-265.
2. Van Dyke T., Jacks T. Cancer modeling in the modern era: progress and challenges. Cell 2002, 108:135-144.
3. Frese K.K., Tuveson D.A. Maximizing mouse cancer models. Nat Rev Cancer 2007, 7:645-658.
4. Walrath J.C., Hawes J.J., Van D.T., Reilly K.M. Genetically engineered mouse models in cancer research. Adv Cancer Res 2010, 106:113-164.
5. Lewandoski M. Conditional control of gene expression in the mouse. Nat Rev Genet 2001, 2:743-755.
6. Heyer J., Kwong L.N., Lowe S.W., Chin L. Non-germline genetically engineered mouse models for translational cancer research. Nat Rev Cancer 2010, 10:470-480.
7. Huijbers I.J., Krimpenfort P., Berns A., Jonkers J. Rapid validation of cancer genes in chimeras derived from established genetically engineered mouse models. Bioessays 2011, 33:701-710.
8. Zhou Y., Rideout W.M., Zi T., Bressel A., Reddypalli S., Rancourt R., Woo J.K., Horner J.W., Chin L., Chiu M.I., et al. Chimeric mouse tumor models reveal differences in pathway activation between ERBB family- and KRAS-dependent lung adenocarcinomas. Nat Biotechnol 2010, 28:71-78.
9. Ying Q.L., Wray J., Nichols J., Batlle-Morera L., Doble B., Woodgett J., Cohen P., Smith A. The ground state of embryonic stem cell self-renewal. Nature 2008, 453:519-523.
10. Premsrirut P.K., Dow L.E., Kim S.Y., Camiolo M., Malone C.D., Miething C., Scuoppo C., Zuber J., Dickins R.A., Kogan S.C., et al. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell 2011, 145:145-158.
11. Edwards S.L., Brough R., Lord C.J., Natrajan R., Vatcheva R., Levine D.A., Boyd J., Reis-Filho J.S., Ashworth A. Resistance to therapy caused by intragenic deletion in BRCA2. Nature 2008, 451:1111-1115.
12. Sakai W., Swisher E.M., Karlan B.Y., Agarwal M.K., Higgins J., Friedman C., Villegas E., Jacquemont C., Farrugia D.J., Couch F.J., et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature 2008, 451:1116-1120.
13. Swisher E.M., Sakai W., Karlan B.Y., Wurz K., Urban N., Taniguchi T. Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance. Cancer Res 2008, 68:2581-2586.
14. Delmore J.E., Issa G.C., Lemieux M.E., Rahl P.B., Shi J., Jacobs H.M., Kastritis E., Gilpatrick T., Paranal R.M., Qi J., et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011, 146:904-917.
15. Zuber J., Shi J., Wang E., Rappaport A.R., Herrmann H., Sison E.A., Magoon D., Qi J., Blatt K., Wunderlich M., et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011, 478:524-528.
16. Jain M., Arvanitis C., Chu K., Dewey W., Leonhardt E., Trinh M., Sundberg C.D., Bishop J.M., Felsher D.W. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 2002, 297:102-104.
17. Shachaf C.M., Kopelman A.M., Arvanitis C., Karlsson A., Beer S., Mandl S., Bachmann M.H., Borowsky A.D., Ruebner B., Cardiff R.D., et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 2004, 431:1112-1117.
18. Sansom O.J., Meniel V.S., Muncan V., Phesse T.J., Wilkins J.A., Reed K.R., Vass J.K., Athineos D., Clevers H., Clarke A.R. Myc deletion rescues Apc deficiency in the small intestine. Nature 2007, 446:676-679.
19. Soucek L., Whitfield J., Martins C.P., Finch A.J., Murphy D.J., Sodir N.M., Karnezis A.N., Swigart L.B., Nasi S., Evan G.I. Modelling Myc inhibition as a cancer therapy. Nature 2008, 455:679-683.
20. Martins C.P., Brown-Swigart L., Evan G.I. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006, 127:1323-1334.
21. Ventura A., Kirsch D.G., McLaughlin M.E., Tuveson D.A., Grimm J., Lintault L., Newman J., Reczek E.E., Weissleder R., Jacks T. Restoration of p53 function leads to tumour regression in vivo. Nature 2007, 445:661-665.
22. Xue W., Zender L., Miething C., Dickins R.A., Hernando E., Krizhanovsky V., Cordon-Cardo C., Lowe S.W. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007, 445:656-660.
23. Junttila M.R., Karnezis A.N., Garcia D., Madriles F., Kortlever R.M., Rostker F., Brown S.L., Pham D.M., Seo Y., Evan G.I., Martins C.P. Selective activation of p53-mediated tumour suppression in high-grade tumours. Nature 2010, 468:567-571.
24. Feldser D.M., Kostova K.K., Winslow M.M., Taylor S.E., Cashman C., Whittaker C.A., Sanchez-Rivera F.J., Resnick R., Bronson R., Hemann M.T., Jacks T. Stage-specific sensitivity to p53 restoration during lung cancer progression. Nature 2010, 468:572-575.
25. Karreth F.A., Tuveson D.A. Modelling oncogenic Ras/Raf signalling in the mouse. Curr Opin Genet Dev 2009, 19:4-11.
26. Blasco R.B., Francoz S., Santamaria D., Canamero M., Dubus P., Charron J., Baccarini M., Barbacid M. c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma. Cancer Cell 2011, 19:652-663.
27. Sharpless N.E., Depinho R.A. The mighty mouse: genetically engineered mouse models in cancer drug development. Nat Rev Drug Discov 2006, 5:741-754.
28. Engelman J.A., Chen L., Tan X., Crosby K., Guimaraes A.R., Upadhyay R., Maira M., McNamara K., Perera S.A., Song Y., et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008, 14:1351-1356.
29. De Raedt T., Walton Z., Yecies J.L., Li D., Chen Y., Malone C.F., Maertens O., Jeong S.M., Bronson R.T., Lebleu V., et al. Exploiting cancer cell vulnerabilities to develop a combination therapy for ras-driven tumors. Cancer Cell 2011, 20:400-413.
30. Singh M., Lima A., Molina R., Hamilton P., Clermont A.C., Devasthali V., Thompson J.D., Cheng J.H., Bou R.H., Ho C.C., et al. Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models. Nat Biotechnol 2010, 28:585-593.
31. Olive K.P., Jacobetz M.A., Davidson C.J., Gopinathan A., McIntyre D., Honess D., Madhu B., Goldgraben M.A., Caldwell M.E., Allard D., et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009, 324:1457-1461.
32. Rottenberg S., Jonkers J. Modeling therapy resistance in genetically engineered mouse cancer models. Drug Resist Updat 2008, 11:51-60.
33. Liu P., Cheng H., Santiago S., Raeder M., Zhang F., Isabella A., Yang J., Semaan D.J., Chen C., Fox E.A., et al. Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms. Nat Med 2011, 17:1116-1120.
34. Bryant H.E., Schultz N., Thomas H.D., Parker K.M., Flower D., Lopez E., Kyle S., Meuth M., Curtin N.J., Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005, 434:913-917.
35. Farmer H., McCabe N., Lord C.J., Tutt A.N., Johnson D.A., Richardson T.B., Santarosa M., Dillon K.J., Hickson I., Knights C., et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005, 434:917-921.
36. Rottenberg S., Jaspers J.E., Kersbergen A., van der B.E., Nygren A.O., Zander S.A., Derksen P.W., de B.M., Zevenhoven J., Lau A., et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A 2008, 105:17079-17084.
37. Hay T., Matthews J.R., Pietzka L., Lau A., Cranston A., Nygren A.O., Douglas-Jones A., Smith G.C., Martin N.M., O'Connor M., Clarke A.R. Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous Brca2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination with carboplatin. Cancer Res 2009, 69:3850-3855.
38. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
39. de Visser K.E., Eichten A., Coussens L.M. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 2006, 6:24-37.
40. de Visser K.E., Korets L.V., Coussens L.M. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 2005, 7:411-423.
41. Andreu P., Johansson M., Affara N.I., Pucci F., Tan T., Junankar S., Korets L., Lam J., Tawfik D., DeNardo D.G., et al. FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell 2010, 17:121-134.
42. DeNardo D.G., Barreto J.B., Andreu P., Vasquez L., Tawfik D., Kolhatkar N., Coussens L.M. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 2009, 16:91-102.
43. Rakhra K., Bachireddy P., Zabuawala T., Zeiser R., Xu L., Kopelman A., Fan A.C., Yang Q., Braunstein L., Crosby E., et al. CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 2010, 18:485-498.
44. Guerra C., Collado M., Navas C., Schuhmacher A.J., Hernandez-Porras I., Canamero M., Rodriguez-Justo M., Serrano M., Barbacid M. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell 2011, 19:728-739.
45. Kessenbrock K., Plaks V., Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010, 141:52-67.
46. Erez N., Truitt M., Olson P., Arron S.T., Hanahan D. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell 2010, 17:135-147.
47. Sodir N.M., Swigart L.B., Karnezis A.N., Hanahan D., Evan G.I., Soucek L. Endogenous Myc maintains the tumor microenvironment. Genes Dev 2011, 25:907-916.
48. Bergers G., Javaherian K., Lo K.M., Folkman J., Hanahan D. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 1999, 284:808-812.
49. Casanovas O., Hicklin D.J., Bergers G., Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 2005, 8:299-309.
50. Paez-Ribes M., Allen E., Hudock J., Takeda T., Okuyama H., Vinals F., Inoue M., Bergers G., Hanahan D., Casanovas O. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009, 15:220-231.
51. Ebos J.M., Lee C.R., Cruz-Munoz W., Bjarnason G.A., Christensen J.G., Kerbel R.S. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009, 15:232-239.
52. Kim C.F., Jackson E.L., Woolfenden A.E., Lawrence S., Babar I., Vogel S., Crowley D., Bronson R.T., Jacks T. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005, 121:823-835.
53. Sutherland K.D., Proost N., Brouns I., Adriaensen D., Song J.Y., Berns A. Cell of origin of small cell lung cancer: inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung. Cancer Cell 2011, 19:754-764.
54. Molyneux G., Geyer F.C., Magnay F.A., McCarthy A., Kendrick H., Natrajan R., Mackay A., Grigoriadis A., Tutt A., Ashworth A., et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 2010, 7:403-417.
55. Barker N., Ridgway R.A., van Es J.H., van de W.M., Begthel H., van den B.M., Danenberg E., Clarke A.R., Sansom O.J., Clevers H. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 2009, 457:608-611.
56. Copeland N.G., Jenkins N.A. Harnessing transposons for cancer gene discovery. Nat Rev Cancer 2010, 10:696-706.