Genetically Engineered Mouse Models of Brain Cancer and the Promise of Preclinical Testing

Brain Pathology - Tập 19 Số 1 - Trang 132-143 - 2009
Jason T. Huse1, Eric C. Holland2
1Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
2Memorial Sloan- Kettering Cancer Center

Tóm tắt

AbstractRecent improvements in the understanding of brain tumor biology have opened the door to a number of rational therapeutic strategies targeting distinct oncogenic pathways. The successful translation of such “designer drugs” to clinical application depends heavily on effective and expeditious screening methods in relevant disease models. By recapitulating both the underlying genetics and the characteristic tumor‐stroma microenvironment of brain cancer, genetically engineered mouse models (GEMMs) may offer distinct advantages over cell culture and xenograft systems in the preclinical testing of promising therapies. This review focuses on recently developed GEMMs for both glioma and medulloblastoma, and discusses their potential use in preclinical trials. Examples showcasing the use of GEMMs in the testing of molecularly targeted therapeutics are given, and relevant topics, such as stem cell biology, in vivo imaging technology and radiotherapy, are also addressed.

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Tài liệu tham khảo

10.5858/2002-126-0540-MAMOAI

10.1097/01.wco.0000189877.31637.74

Bajenaru ML, 2003, Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity, Cancer Res, 63, 8573

10.1002/ana.20337

10.1158/0008-5472.CAN-05-3827

10.1158/0008-5472.CAN-07-6350

10.1158/0008-5472.CAN-05-2198

10.1093/jnci/90.19.1473

10.1016/j.ccr.2006.11.020

10.1038/nature07385

10.1158/0008-5472.CAN-06-1193

10.1101/gad.903001

10.1097/00006123-199802000-00080

Ding H, 2001, Astrocyte‐specific expression of activated p21‐ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas, Cancer Res, 61, 3826

Ding H, 2003, Oligodendrogliomas result from the expression of an activated mutant epidermal growth factor receptor in a ras transgenic mouse astrocytoma model, Cancer Res, 63, 1106

10.1158/1078-0432.CCR-06-0438

10.1038/sj.emboj.7601703

Frederick L, 2000, Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas, Cancer Res, 60, 1383

Friedman JM, 1999, Neurofibromatosis: Phenotype, Natural History, and Pathogenesis

10.1101/gad.1596707

10.1016/S1470-2045(04)01424-X

Gilbertson RJ, 2008, The origins of medulloblastoma subtypes. Annu Rev, Pathol, 3, 341

10.1126/science.277.5329.1109

10.1038/sj.onc.1201455

10.1016/S0092-8674(00)81268-4

10.1158/0008-5472.CAN-04-1813

10.1101/gad.1627008

10.1158/0008-5472.CAN-07-5092

10.1158/0008-5472.CAN-07-5916

10.1002/ana.410360505

10.1038/sj.onc.1209704

10.1073/pnas.95.3.1218

10.1101/gad.12.23.3675

10.1038/75596

10.1158/0008-5472.CAN-05-1173

10.1593/neo.04595

10.1385/1-59259-843-9:019

James CD, 1988, Clonal genomic alterations in glioma malignancy stages, Cancer Res, 48, 5546

10.1242/dev.00182

10.1016/j.ccr.2008.01.027

10.1158/0008-5472.CAN-07-6867

10.1038/sj.onc.1210467

Lee Y, 2002, DNA ligase IV suppresses medulloblastoma formation, Cancer Res, 62, 6395

10.1158/0008-5472.CAN-06-0505

10.1097/00005072-199401000-00002

10.1126/science.1978757

10.1158/0008-5472.CAN-06-0657

10.1101/gad.14.8.994

10.1158/0008-5472.CAN-06-4177

10.1158/0008-5472.CAN-05-1042

10.1385/1-59259-843-9:033

10.1093/jnci/djg072

10.1126/science.1164382

10.1038/sj.onc.1205973

10.1038/sj.onc.1209032

10.1016/j.ccr.2006.02.019

Pietsch T, 1997, Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched, Cancer Res, 57, 2085

10.1038/415436a

Raffel C, 1997, Sporadic medulloblastomas contain PTCH mutations, Cancer Res, 57, 842

10.1016/S1476-5586(03)80052-0

10.1038/sj.onc.1207818

Reifenberger G, 1994, Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p, Am J Pathol, 145, 1175

Reifenberger J, 1998, Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system, Cancer Res, 58, 1798

10.1038/79075

10.1158/0008-5472.CAN-08-0703

10.1016/j.ccr.2004.08.019

10.1158/1078-0432.CCR-07-2072

10.1158/0008-5472.CAN-05-4505

10.1016/j.ccr.2008.07.005

10.1016/S0002-9440(10)62057-3

10.1038/nrd2110

10.1158/0008-5472.CAN-03-3831

Singh SK, 2003, Indentification of a cancer stem cell in human brain tumors, Cancer Res, 63, 5821

10.1056/NEJMoa043330

10.1038/ng916

10.1016/S0025-6196(12)62221-6

Ueki K, 1996, CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated, Cancer Res, 56, 150

Uhrbom L, 1998, Induction of brain tumors in mice using a recombinant platelet‐derived growth factor b‐chain retrovirus, Cancer Res, 58, 5275

Uhrbom L, 2002, Ink4a‐Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt, Cancer Res, 62, 5551

10.1038/nm1120

10.1101/gad.1368605

10.1038/labinvest.3700123

10.1093/jnen/60.12.1181

10.1158/0008-5472.CAN-06-0712

Weiss WA, 2003, Genetic determinants of malignancy in a mouse model for oligodendroglioma, Cancer Res, 63, 1589

10.1056/NEJMra0708126

10.1002/glia.440150307

Wetmore C, 2000, The normal patched allele is expressed in medulloblastomas from mice with heterozygous germ‐line mutation of patched, Cancer Res, 60, 2239

Wetmore C, 2001, Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched, Cancer Res, 61, 513

10.1073/pnas.89.7.2965

Wu JK, 1990, DIfferential expression of ros oncogene in primary human astrocytomas and astrocytoma cell lines, Cancer Res, 50, 3032

10.1016/S1535-6108(02)00029-6

10.1158/0008-5472.CAN-04-3902

10.1073/pnas.0601938103

10.1016/j.ccr.2008.07.003

10.1016/j.ccr.2005.07.004

10.1242/dev.02162

10.1002/(SICI)1098-2264(200005)28:1<77::AID-GCC9>3.0.CO;2-Y