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

Amrita Basu, Nicole E. Bodycombe, Jaime H. Cheah, Edmund V. Price, Ke Liu, Giannina I. Schaefer, Richard Y. Ebright, Michelle L. Stewart, Daisuke Ito, Stephanie Wang, Abigail L. Bracha, Ted Liefeld, Mathias Wawer, Joshua C. Gilbert, Andrew J. Wilson, Nicolas Stransky, Gregory V. Kryukov, Vlado Dancik, Jordi Barretina, Levi A. GarrawayC. Suk Yee Hon, Benito Munoz, Joshua A. Bittker, Brent R. Stockwell, Dineo Khabele, Andrew M. Stern, Paul A. Clemons, Alykhan F. Shamji, Stuart L. Schreiber

Research output: Contribution to journalArticlepeer-review

419 Scopus citations

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 β-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.

Original languageEnglish
Pages (from-to)X1151-1161
JournalCell
Volume154
Issue number5
DOIs
StatePublished - Aug 29 2013

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