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An interactive resource to identify cancer genetic and lineage dependencies targeted by small molecules

Basu, A and Bodycombe, NE and Cheah, JH and Price, EV and Liu, K and Schaefer, GI and Ebright, RY and Stewart, ML and Ito, D and Wang, S and Bracha, AL and Liefeld, T and Wawer, M and Gilbert, JC and Wilson, AJ and Stransky, N and Kryukov, GV and Dancik, V and Barretina, J and Garraway, LA and Hon, CSY and Munoz, B and Bittker, JA and Stockwell, BR and Khabele, D and Stern, AM and Clemons, PA and Shamji, AF and Schreiber, SL (2013) An interactive resource to identify cancer genetic and lineage dependencies targeted by small molecules. Cell. pp. 1151-1161.

Abstract

The high rate of clinical response to protein-kinase-targeting drugs matched to cancer patients with specific genomic alterations has prompted efforts to use cancer cell line (CCL) profiling to identify additional biomarkers of small-molecule sensitivities. We have quantitatively measured the sensitivity of 242 genomically characterized CCLs to an Informer Set of 354 small molecules that target many nodes in cell circuitry, uncovering protein dependencies that: (1) associate with specific cancer-genomic alterations and (2) can be targeted by small molecules. We have created the Cancer Therapeutics Response Portal (http://www.broadinstitute.org/ctrp) to enable users to correlate genetic features to sensitivity in individual lineages and control for confounding factors of CCL profiling. We report a candidate dependency, associating activating mutations in the oncogene beta-catenin with sensitivity to the Bcl-2 family antagonist, navitoclax. The resource can be used to develop novel therapeutic hypotheses and to accelerate discovery of drugs matched to patients by their cancer genotype and lineage. 2013 Elsevier Inc

Item Type: Article
Additional Information: pubid: 22 nvp_institute: NIBR contributor_address: (Basu, Bodycombe, Cheah, Price, Liu, Schaefer, Ebright, Stewart, Ito, Wang, Bracha, Liefeld, Wawer, Gilbert, Stransky, Kryukov, Dancik, Barretina, Garraway, Hon, Munoz, Bittker, Stern, Clemons, Shamji, Schreiber) Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States (Wilson, Khabele) Vanderbilt University School of Medicine, Nashville, TN 37232, United States (Stockwell) Columbia University, New York, NY 10027, United States (Ito) H3 Biomedicine, Cambridge, MA 02139, United States (Stransky) Blueprint Medicines, Cambridge, MA 02142, United States (Barretina) Novartis Institutes for Biomedical Research (NIBR), Cambridge, MA 02139, United States
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21874

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