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Off-the-shelf models of chromosomal translocations and using antibody fragments as cancer drug surrogates

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Chromosomal translocations are primary somatic events found in all forms of cancer, ranging from leukaemia/lymphomas, sarcomas and epithelial tumours. This kind of genomic disturbance has major consequences in cancer initiating cells, often through the creation of a gene fusion or by altered gene expression through abnormal transcriptional contexts. The protein products of chromosomal translocations are intracellular and often function through protein-protein interaction in the cytoplasm or nucleus of cancer cells. We are translating these findings into therapeutic applications by developing pre-clinical models of human cancer and targeting cancer-associated protein-protein interactions for drug target validation. I will describe our “fast throughput” mouse cancer modeling enabling recapitulation of corresponding human cancers for pre-clinical studies. We are using such models to evaluate the efficacy of antibody fragments as drug surrogates. Preliminary data will be presented about the use of structure/function-based methods to develop chemical compounds that mimic the critical binding residues of antibody fragments (small molecule emulators of antibody binding sites) as leads for anti-cancer drug development.

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