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

Cell
Authors
Keywords
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.

Year of Publication
2013
Journal
Cell
Volume
154
Issue
5
Pages
1151-1161
Date Published
2013 Aug 29
ISSN
1097-4172
URL
DOI
10.1016/j.cell.2013.08.003
PubMed ID
23993102
PubMed Central ID
PMC3954635
Links
Grant list
RC2 CA148399 / CA / NCI NIH HHS / United States
R01 CA161061 / CA / NCI NIH HHS / United States
K08 CA148887 / CA / NCI NIH HHS / United States
RC2-CA148399 / CA / NCI NIH HHS / United States
R01 CA097061 / CA / NCI NIH HHS / United States