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- W2332873313 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCThe explosion of knowledge regarding the genetic underpinnings of human cancer heralds a new era of targeted therapy. To date, in vivo cell based screening has proven a useful tool in almost all drug development programs. Cells used in such screens are usually harvested from cancer patients that harbor the specific mutation of interest, but these cells almost invariably contain many other additional mutations making it difficult to ascertain the specific functions of molecules being screened. Thus the lack of true control cells hampers the development of new cancer therapeutics.Using cell lines generated with Horizon Discovery's proprietary rAAV-based GENESIS™ gene editing platform, we have established a comprehensive range of isogenic cancer models for our in vivo compound screening program to service our clients in academia and industry, with mutations in a wide variety of genes including KRAS, PIK3CA, PTEN, IDH1 and p53. These isogenic tumor models comprise pairs of cell lines which share the same genetic background, differing only by the mutation of interest and therefore allowing definitive studies of specific genetic variances to be performed. The same isogenic pairs of lines can be used for in vitro and in vivo experiments to ensure continuity and relevance of results. We have carried out intensive validation of these models in vivo to ensure the lines generate robust tumor growth in mice and the matched tumors differ only in the genetic composition of target gene.In a POC study, colon cancer cell lines with the KRAS G13D mutation have been demonstrated to respond to Cetuximab treatment, consistent with recent findings in the clinic. These results challenge the current clinical practice of only using Cetuximab as a therapeutic for KRAS wild type patients, and provide the basis for expanding the usage of the drug to benefit more patients.In summary, we have established a series of reliable in vivo isogenic models with precise and highly specific genetic modifications as predictors of clinical effect. They will provide a valuable tool in the drug discovery and development arena to drive forward personalized medicine by enabling novel target validation, expansion of the target population for existing therapeutics, and definition of patient responsive genotypes.Citation Format: Yanmei Sun, Songling Zhang, Holly Astley, Rebecca Foster, Christine Schofield, Chris Torrance, Jinying Ning, Taiping Chen, Qian Shi. Utilization of in vivo human isogenic cancer models in the new era of targeted therapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2782. doi:10.1158/1538-7445.AM2013-2782" @default.
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- W2332873313 date "2013-04-15" @default.
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- W2332873313 title "Abstract 2782: Utilization ofin vivohuman isogenic cancer models in the new era of targeted therapies." @default.
- W2332873313 doi "https://doi.org/10.1158/1538-7445.am2013-2782" @default.
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