Cell
Volume 154, Issue 5, 29 August 2013, Pages 1151-1161
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An Interactive Resource to Identify Cancer Genetic and Lineage Dependencies Targeted by Small Molecules

https://doi.org/10.1016/j.cell.2013.08.003Get rights and content
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Highlights

  • A therapeutics resource identifies cancer genotype-compound sensitivity relationships

  • Genetic features of cancer cell lines correlate with their response to compounds

  • The resource controls for possible confounding factors of genomic cell-line profiling

  • Results suggest a strategy for treating cancers with mutations in β-catenin

Summary

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.

Cited by (0)

4

These authors contributed equally to this work

5

Present address: H3 Biomedicine, Cambridge, MA 02139, USA

6

Present address: Blueprint Medicines, Cambridge, MA 02142, USA

7

Present address: Novartis Institutes for Biomedical Research (NIBR), Cambridge, MA 02139, USA