Abstract
Preclinical evaluation of candidate anticancer compounds requires appropriate animal models. Most commonly, solid tumor xenograft systems are employed in which immunocompromised mice are implanted with human cancer cell lines. Genetically engineered mouse models of solid tumors are also frequently employed. Both of these approaches can also be applied to studies of hematological malignancies. In this chapter, we describe three types of mouse models of leukemia driven by the human BCR-ABL oncogene. We also discuss the application of these models to preclinical testing of active-site TOR inhibitors, a novel class of compounds that selectively target the ATP-binding pocket of the target of rapamycin (TOR) kinase.
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Acknowledgments
The authors would like to thank Christian Rommel, Yi Liu, Pingda Ren, and Troy Wilson for the chemical synthesis and technical support with PP242 before it was commercially available. We also thank Andrew Miller for technical advice with NSG mice and Collin Vu for experimental assistance with primary human xenografts. We thank Marina Konopleva and Michael Lilly for access to primary human leukemia samples. Studies of TOR inhibitors in our laboratory have been supported by Intellikine, Inc., and by a Discovery Grant from the University of California Industry-University Cooperative Research Program.
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Janes, M.R., Fruman, D.A. (2012). The In Vivo Evaluation of Active-Site TOR Inhibitors in Models of BCR-ABL+ Leukemia. In: Weichhart, T. (eds) mTOR. Methods in Molecular Biology, vol 821. Humana Press. https://doi.org/10.1007/978-1-61779-430-8_15
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DOI: https://doi.org/10.1007/978-1-61779-430-8_15
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