Abstract
Proper target selection and validation are crucial to the discovery of new anti-cancer agents. Since tumors depend on a suitable microenvironment for their growth, once a putative target has been identified, its validation should be performed whenever possible in vivo. This chapter deals with the generation of human xenograft mouse models genetically modified to induce the modulation of cancer-related genes as an approach to validate oncology targets.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Iorns E, Lord CJ, Turner N, Ashworth A (2007) Utilizing RNA interference to enhance cancer drug discovery. Nat Rev Drug Discov 6:556–568
Sandy P, Ventura A, Jacks T (2005) Mammalian RNAi: a practical guide. Biotechniques 39:215–224
Rankin EB, Fuh KC, Taylor TE et al (2010) AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res 70:7570–7579
Costa C, Hirsch E (2011) More than just kinases: the scaffolding function of PI3K. Curr Top Microbiol Immunol 346:171–181
Morgan-Lappe SE, Tucker LA, Huang X et al (2007) Identification of Ras-related nuclear protein, targeting protein for xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen. Cancer Res 67:4390–4398
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674
Singh M, Johnson L (2006) Using genetically engineered mouse models of cancer to aid drug development: an industry perspective. Clin Cancer Res 12:5312–5328
Elez R, Piiper A, Kronenberger B et al (2003) Tumor regression by combination antisense therapy against Plk1 and Bcl-2. Oncogene 22:69–80
Futami K, Kumagai E, Makino H et al (2008) Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models. Cancer Sci 99:1227–1236
Oh BY, Lee RA, Kim KH (2011) siRNA targeting Livin decreases tumor in a xenograft model for colon cancer. World J Gastroenterol 17:2563–2571
Verma UN, Surabhi RM, Schmaltieg A et al (2003) Small interfering RNAs directed against beta-catenin inhibit the in vitro and in vivo growth of colon cancer cells. Clin Cancer Res 9:1291–1300
Oliveira S, Storm G, Schiffelers RM (2006) Targeted delivery of siRNA. J Biomed Biotechnol 2006:63675
Barres V, Ouellet V, Lafontaine J et al (2011) An essential role for Ran GTPase in epithelial ovarian cancer cell survival. Mol Cancer 9:272
Ganzinelli M, Carrassa L, Crippa F et al (2008) Checkpoint kinase 1 down-regulation by an inducible small interfering RNA expression system sensitized in vivo tumors to treatment with 5-fluorouracil. Clin Cancer Res 14:5131–5141
Lee-Hoeflich ST, Crocker L, Yao E et al (2008) A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res 68:5878–5887
Sala G, Dituri F, Raimondi C et al (2008) Phospholipase Cgamma1 is required for metastasis development and progression. Cancer Res 68:10187–10196
Feng M, Zhang J, Anver M et al (2011) In vivo imaging of human malignant mesothelioma grown orthotopically in the peritoneal cavity of nude mice. J Cancer 2:123–131
Wang M, Gartel AL (2011) The suppression of FOXM1 and its targets in breast cancer xenograft tumors by siRNA. Oncotarget 2:1218–1226
Choy G, Choyke P, Libutti SK (2003) Current advances in molecular imaging: noninvasive in vivo bioluminescent and fluorescent optical imaging in cancer research. Mol Imaging 2:303–312
Luker GD, Luker KE (2008) Optical imaging: current applications and future directions. J Nucl Med 49:1–4
Richmond A, Su Y (2008) Mouse xenograft models vs GEM models for human cancer therapeutics. Dis Model Mech 1:78–82
Hillen W, Berens C (1994) Mechanisms underlying expression of Tn10 encoded tetracycline resistance. Annu Rev Microbiol 48:345–369
Hillen W, Gatz C, Altschmied L et al (1983) Control of expression of the Tn10-encoded tetracycline resistance genes. Equilibrium and kinetic investigation of the regulatory reaction. J Mol Biol 169:707–721
Yao F, Svensjo T, Winkler T et al (1998) Tetracycline repressor, tetR, rather than the tetR-mammalian cell transcription factor fusion derivatives, regulates inducible gene expression in mammalian cells. Hum Gene Ther 9:1939–1950
Marrazzo E, Marchini S, Previdi S et al (2006) Questioning the oncogenic role of DeltaNp73alpha in different cell lines expressing p53 or not. Cancer Biol Ther 5:794–803
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 SpringerScience+Business Media New York
About this protocol
Cite this protocol
Mazzoletti, M., Texidó, G. (2013). In Vivo Target Validation by Inducible RNAi in Human Xenograft Mouse Models. In: Moll, J., Colombo, R. (eds) Target Identification and Validation in Drug Discovery. Methods in Molecular Biology, vol 986. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-311-4_20
Download citation
DOI: https://doi.org/10.1007/978-1-62703-311-4_20
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-310-7
Online ISBN: 978-1-62703-311-4
eBook Packages: Springer Protocols