Abstract
Drug discovery and development are often hampered by lack of target identification and clinical tractability. Repurposing of approved drugs to life-threatening diseases such as leukemia is emerging as a promising alternative approach. Connectivity mapping systems link approved drugs with disease-related gene signatures. Relevant preclinical models provide essential tools for system validation and proof-of-concept studies. Herein we describe procedures aimed at generating disease-based gene signatures and applying them to established cross-referencing databases of potential candidate drugs. As a proof of principle, we present the identification of Entinostat as a candidate drug for the treatment of HOX-TALE-related leukemia.
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Acknowledgements
The authors would like to thank the staff within the Biological Resource Unit and Bioinformatics Cores, Queen’s University Belfast. Alex Thompson is a recipient of the American Cancer Society for Beginning Investigator Fellowship from the UICC. This work was supported by grants from Leukemia Lymphoma Research, UK (07016 and 09035), the Leukaemia Lymphoma Northern Ireland (LLNI), and Biotechnology and Biological Science Research Council (BBSRC).
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Kettyle, L.M.J., Liberante, F.G., Thompson, A. (2014). Rational Drug Repurposing Using sscMap Analysis in a HOX-TALE Model of Leukemia. In: Graba, Y., Rezsohazy, R. (eds) Hox Genes. Methods in Molecular Biology, vol 1196. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1242-1_21
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DOI: https://doi.org/10.1007/978-1-4939-1242-1_21
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