Skip to main content
Top
Published in: Radiation Oncology 1/2012

Open Access 01-12-2012 | Review

Preclinical models in radiation oncology

Authors: Jenna Kahn, Philip J Tofilon, Kevin Camphausen

Published in: Radiation Oncology | Issue 1/2012

Login to get access

Abstract

As the incidence of cancer continues to rise, the use of radiotherapy has emerged as a leading treatment modality. Preclinical models in radiation oncology are essential tools for cancer research and therapeutics. Various model systems have been used to test radiation therapy, including in vitro cell culture assays as well as in vivo ectopic and orthotopic xenograft models. This review aims to describe such models, their advantages and disadvantages, particularly as they have been employed in the discovery of molecular targets for tumor radiosensitization. Ultimately, any model system must be judged by its utility in developing more effective cancer therapies, which is in turn dependent on its ability to simulate the biology of tumors as they exist in situ. Although every model has its limitations, each has played a significant role in preclinical testing. Continued advances in preclinical models will allow for the identification and application of targets for radiation in the clinic.
Appendix
Available only for authorised users
Literature
3.
go back to reference Hall EJ: Radiobiology for the radiologist. 7th edition. Philadelphia: Lippincott Williams and Wilkins; 2011. Hall EJ: Radiobiology for the radiologist. 7th edition. Philadelphia: Lippincott Williams and Wilkins; 2011.
4.
go back to reference Camphausen K, Cerna D, Scott T, Sproull M, Burgan WE, Cerra MA, Fine H, Tofilon PJ: Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid. Int J Cancer J Int du cancer 2005,114(3):380-386. 10.1002/ijc.20774CrossRef Camphausen K, Cerna D, Scott T, Sproull M, Burgan WE, Cerra MA, Fine H, Tofilon PJ: Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid. Int J Cancer J Int du cancer 2005,114(3):380-386. 10.1002/ijc.20774CrossRef
5.
go back to reference Mehrian Shai R, Reichardt JK, Ya-Hsuan H, Kremen TJ, Liau LM, Cloughesy TF, Mischel PS, Nelson S, Mehrian Shai R, Reichardt JK, Ya-Hsuan H, Kremen TJ, Liau LM, Cloughesy TF, Mischel PS, Nelson SF: Robustness of gene expression profiling in glioma specimen samplings and derived cell lines. Brain Res Mol Brain Res 2005,136(1-2):99-103. 10.1016/j.molbrainres.2005.01.017CrossRefPubMed Mehrian Shai R, Reichardt JK, Ya-Hsuan H, Kremen TJ, Liau LM, Cloughesy TF, Mischel PS, Nelson S, Mehrian Shai R, Reichardt JK, Ya-Hsuan H, Kremen TJ, Liau LM, Cloughesy TF, Mischel PS, Nelson SF: Robustness of gene expression profiling in glioma specimen samplings and derived cell lines. Brain Res Mol Brain Res 2005,136(1-2):99-103. 10.1016/j.molbrainres.2005.01.017CrossRefPubMed
6.
go back to reference McAllister SS, Weinberg RA: Tumor-host interactions: a far-reaching relationship. J Clin Oncol 2010,28(26):4022-4028. 10.1200/JCO.2010.28.4257CrossRefPubMed McAllister SS, Weinberg RA: Tumor-host interactions: a far-reaching relationship. J Clin Oncol 2010,28(26):4022-4028. 10.1200/JCO.2010.28.4257CrossRefPubMed
7.
go back to reference Fomchenko EI, Holland EC: Mouse models of brain tumors and their applications in preclinical trials. Clin Cancer Res 2006,12(18):5288-5297. 10.1158/1078-0432.CCR-06-0438CrossRefPubMed Fomchenko EI, Holland EC: Mouse models of brain tumors and their applications in preclinical trials. Clin Cancer Res 2006,12(18):5288-5297. 10.1158/1078-0432.CCR-06-0438CrossRefPubMed
8.
go back to reference Kirsch DG, Santiago PM, di Tomaso E, Sullivan JM, Hou WS, Dayton T, Jeffords LB, Sodha P, Mercer KL, Cohen R, et al.: p53 Controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science 2010,327(5965):593-596. 10.1126/science.1166202PubMedCentralCrossRefPubMed Kirsch DG, Santiago PM, di Tomaso E, Sullivan JM, Hou WS, Dayton T, Jeffords LB, Sodha P, Mercer KL, Cohen R, et al.: p53 Controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science 2010,327(5965):593-596. 10.1126/science.1166202PubMedCentralCrossRefPubMed
9.
go back to reference Yoon SS, Stangenberg L, Lee YJ, Rothrock C, Dreyfuss JM, Baek KH, Waterman PR, Nielsen GP, Weissleder R, Mahmood U, et al.: Efficacy of sunitinib and radiotherapy in genetically engineered mouse model of soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 2009,74(4):1207-1216. 10.1016/j.ijrobp.2009.02.052PubMedCentralCrossRefPubMed Yoon SS, Stangenberg L, Lee YJ, Rothrock C, Dreyfuss JM, Baek KH, Waterman PR, Nielsen GP, Weissleder R, Mahmood U, et al.: Efficacy of sunitinib and radiotherapy in genetically engineered mouse model of soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 2009,74(4):1207-1216. 10.1016/j.ijrobp.2009.02.052PubMedCentralCrossRefPubMed
10.
go back to reference Rygaard J, Povlsen CO: Heterotransplantation of a human malignant tumour to "nude" mice. Acta Pathol Microbiol Scand 1969,77(4):758-760.CrossRefPubMed Rygaard J, Povlsen CO: Heterotransplantation of a human malignant tumour to "nude" mice. Acta Pathol Microbiol Scand 1969,77(4):758-760.CrossRefPubMed
11.
go back to reference Banuelos CA, Banath JP, MacPhail SH, Zhao J, Eaves CA, O'Connor MD, Lansdorp PM, Olive PL: Mouse but not human embryonic stem cells are deficient in rejoining of ionizing radiation-induced DNA double-strand breaks. DNA Repair 2008,7(9):1471-1483. 10.1016/j.dnarep.2008.05.005CrossRefPubMed Banuelos CA, Banath JP, MacPhail SH, Zhao J, Eaves CA, O'Connor MD, Lansdorp PM, Olive PL: Mouse but not human embryonic stem cells are deficient in rejoining of ionizing radiation-induced DNA double-strand breaks. DNA Repair 2008,7(9):1471-1483. 10.1016/j.dnarep.2008.05.005CrossRefPubMed
12.
go back to reference Kramp TR, Camphausen K: Combination radiotherapy in an orthotopic mouse brain tumor model. JoVE 2012, 61: e3397.PubMed Kramp TR, Camphausen K: Combination radiotherapy in an orthotopic mouse brain tumor model. JoVE 2012, 61: e3397.PubMed
13.
go back to reference Camphausen K, Purow B, Sproull M, Scott T, Ozawa T, Deen DF, Tofilon PJ: Influence of in vivo growth on human glioma cell line gene expression: convergent profiles under orthotopic conditions. Proc Natl Acad Sci U S A 2005,102(23):8287-8292. 10.1073/pnas.0502887102PubMedCentralCrossRefPubMed Camphausen K, Purow B, Sproull M, Scott T, Ozawa T, Deen DF, Tofilon PJ: Influence of in vivo growth on human glioma cell line gene expression: convergent profiles under orthotopic conditions. Proc Natl Acad Sci U S A 2005,102(23):8287-8292. 10.1073/pnas.0502887102PubMedCentralCrossRefPubMed
14.
go back to reference Greenaway J, Moorehead R, Shaw P, Petrik J: Epithelial-stromal interaction increases cell proliferation, survival and tumorigenicity in a mouse model of human epithelial ovarian cancer. Gynecol Oncol 2008,108(2):385-394. 10.1016/j.ygyno.2007.10.035CrossRefPubMed Greenaway J, Moorehead R, Shaw P, Petrik J: Epithelial-stromal interaction increases cell proliferation, survival and tumorigenicity in a mouse model of human epithelial ovarian cancer. Gynecol Oncol 2008,108(2):385-394. 10.1016/j.ygyno.2007.10.035CrossRefPubMed
15.
go back to reference Annabi B, Rojas-Sutterlin S, Laflamme C, Lachambre MP, Rolland Y, Sartelet H, Beliveau R: Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res: MCR 2008,6(6):907-916. 10.1158/1541-7786.MCR-07-2184CrossRefPubMed Annabi B, Rojas-Sutterlin S, Laflamme C, Lachambre MP, Rolland Y, Sartelet H, Beliveau R: Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res: MCR 2008,6(6):907-916. 10.1158/1541-7786.MCR-07-2184CrossRefPubMed
16.
go back to reference Gelbard A, Kupferman ME, Jasser SA, Chen W, El-Naggar AK, Myers JN, Hanna EY: An orthotopic murine model of sinonasal malignancy. Clin Cancer Res 2008,14(22):7348-7357. 10.1158/1078-0432.CCR-08-0977CrossRefPubMed Gelbard A, Kupferman ME, Jasser SA, Chen W, El-Naggar AK, Myers JN, Hanna EY: An orthotopic murine model of sinonasal malignancy. Clin Cancer Res 2008,14(22):7348-7357. 10.1158/1078-0432.CCR-08-0977CrossRefPubMed
17.
go back to reference Li B, Torossian A, Li W, Schleicher S, Niu K, Giacalone NJ, Kim SJ, Chen H, Gonzalez A, Moretti L, et al.: A novel bioluminescence orthotopic mouse model for advanced lung cancer. Radiat Res 2011,176(4):486-493. 10.1667/RR2565.1PubMedCentralCrossRefPubMed Li B, Torossian A, Li W, Schleicher S, Niu K, Giacalone NJ, Kim SJ, Chen H, Gonzalez A, Moretti L, et al.: A novel bioluminescence orthotopic mouse model for advanced lung cancer. Radiat Res 2011,176(4):486-493. 10.1667/RR2565.1PubMedCentralCrossRefPubMed
18.
go back to reference Camphausen K, Purow B, Sproull M, Scott T, Ozawa T, Deen DF, Tofilon PJ: Orthotopic growth of human glioma cells quantitatively and qualitatively influences radiation-induced changes in gene expression. Cancer Res 2005,65(22):10389-10393. 10.1158/0008-5472.CAN-05-1904CrossRefPubMed Camphausen K, Purow B, Sproull M, Scott T, Ozawa T, Deen DF, Tofilon PJ: Orthotopic growth of human glioma cells quantitatively and qualitatively influences radiation-induced changes in gene expression. Cancer Res 2005,65(22):10389-10393. 10.1158/0008-5472.CAN-05-1904CrossRefPubMed
19.
go back to reference Lamfers ML, Idema S, Bosscher L, Heukelom S, Moeniralm S, van der Meulen-Muileman IH, Overmeer RM, van der Valk P, van Beusechem VW, Gerritsen WR, et al.: Differential effects of combined Ad5- delta 24RGD and radiation therapy in in vitro versus in vivo models of malignant glioma. Clin Cancer Res 2007,13(24):7451-7458. 10.1158/1078-0432.CCR-07-1265CrossRefPubMed Lamfers ML, Idema S, Bosscher L, Heukelom S, Moeniralm S, van der Meulen-Muileman IH, Overmeer RM, van der Valk P, van Beusechem VW, Gerritsen WR, et al.: Differential effects of combined Ad5- delta 24RGD and radiation therapy in in vitro versus in vivo models of malignant glioma. Clin Cancer Res 2007,13(24):7451-7458. 10.1158/1078-0432.CCR-07-1265CrossRefPubMed
20.
go back to reference Lee CJ, Spalding AC, Ben-Josef E, Wang L, Simeone DM: In vivo bioluminescent imaging of irradiated orthotopic pancreatic cancer xenografts in nonobese diabetic-severe combined immunodeficient mice: a novel method for targeting and assaying efficacy of ionizing radiation. Transl Oncol 2010,3(3):153-159.PubMedCentralCrossRefPubMed Lee CJ, Spalding AC, Ben-Josef E, Wang L, Simeone DM: In vivo bioluminescent imaging of irradiated orthotopic pancreatic cancer xenografts in nonobese diabetic-severe combined immunodeficient mice: a novel method for targeting and assaying efficacy of ionizing radiation. Transl Oncol 2010,3(3):153-159.PubMedCentralCrossRefPubMed
21.
go back to reference Bredel M, Bredel C, Juric D, Harsh GR, Vogel H, Recht LD, Sikic BI: High-resolution genome-wide mapping of genetic alterations in human glial brain tumors. Cancer Res 2005,65(10):4088-4096. 10.1158/0008-5472.CAN-04-4229CrossRefPubMed Bredel M, Bredel C, Juric D, Harsh GR, Vogel H, Recht LD, Sikic BI: High-resolution genome-wide mapping of genetic alterations in human glial brain tumors. Cancer Res 2005,65(10):4088-4096. 10.1158/0008-5472.CAN-04-4229CrossRefPubMed
22.
go back to reference Comprehensive genomic characterization defines human glioblastoma genes and core pathways Nature 2008,455(7216):1061-1068. 10.1038/nature07385 Comprehensive genomic characterization defines human glioblastoma genes and core pathways Nature 2008,455(7216):1061-1068. 10.1038/nature07385
23.
go back to reference Shankavaram UT, Bredel M, Burgan WE, Carter D, Tofilon P, Camphausen K: Molecular profiling indicates orthotopic xenograft of glioma cell lines simulate a subclass of human glioblastoma. J Cell Mol Med 2012,16(3):545-554. 10.1111/j.1582-4934.2011.01345.xPubMedCentralCrossRefPubMed Shankavaram UT, Bredel M, Burgan WE, Carter D, Tofilon P, Camphausen K: Molecular profiling indicates orthotopic xenograft of glioma cell lines simulate a subclass of human glioblastoma. J Cell Mol Med 2012,16(3):545-554. 10.1111/j.1582-4934.2011.01345.xPubMedCentralCrossRefPubMed
Metadata
Title
Preclinical models in radiation oncology
Authors
Jenna Kahn
Philip J Tofilon
Kevin Camphausen
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2012
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-7-223

Other articles of this Issue 1/2012

Radiation Oncology 1/2012 Go to the issue