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Oncogene. 2013 Aug 15;32(33):3809-18. doi: 10.1038/onc.2012.389. Epub 2012 Sep 10.

Gene signature critical to cancer phenotype as a paradigm for anticancer drug discovery.

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  • 1Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.


Malignant cell transformation commonly results in the deregulation of thousands of cellular genes, an observation that suggests a complex biological process and an inherently challenging scenario for the development of effective cancer interventions. To better define the genes/pathways essential to regulating the malignant phenotype, we recently described a novel strategy based on the cooperative nature of carcinogenesis that focuses on genes synergistically deregulated in response to cooperating oncogenic mutations. These so-called 'cooperation response genes' (CRGs) are highly enriched for genes critical for the cancer phenotype, thereby suggesting their causal role in the malignant state. Here, we show that CRGs have an essential role in drug-mediated anticancer activity and that anticancer agents can be identified through their ability to antagonize the CRG expression profile. These findings provide proof-of-concept for the use of the CRG signature as a novel means of drug discovery with relevance to underlying anticancer drug mechanisms.

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