Identifying and targeting cancer dependencies with small molecules

The Cancer Therapeutics Response Portal (CTRP) links genetic, lineage, and other cellular features of cancer cell lines to small-molecule sensitivity with the goal of accelerating discovery of patient-matched cancer therapeutics.
   We generated an 'Informer Set' of 481 small-molecule probes and drugs that selectively target distinct nodes in cell circuitry and that collectively modulate a broad array of cell processes. We quantitatively measured the sensitivity of 860 deeply characterized cancer-cell lines to Informer Set compounds, and have undertaken analyses connecting sensitivity to cancer features, including mutations, gene expression, copy-number variation, and lineage. These analyses, and links to the underlying data, are provided openly on the CTRP.
   The CTRP is a living resource for the biomedical research community that can be mined to develop insights into small-molecule mechanisms of action and novel therapeutic hypotheses, and to support future discovery of drugs matched to patients based on predictive biomarkers.

   Publications

Please cite our cancer cell-line profiling Resource by referencing:
"Correlating chemical sensitivity and basal gene expression reveals mechanism of action" Rees et al., Nat Chem Biol, 12, 109-116 (2016), and
"Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset" Seashore-Ludlow et al., Cancer Discovery, 5, 1210-1223 (2015), and
"An Interactive Resource to Identify Cancer Genetic and Lineage Dependencies Targeted by Small Molecules" Basu, Bodycombe, Cheah, et al., Cell, 154, 1151-1161 (2013).

   Acknowledgements

The Cancer Therapeutics Response Portal was developed by researchers at the Center for the Science of Therapeutics at the Broad Institute and is sponsored in part by the NCI's Cancer Target Discovery and Development Network.

   Complementary Resources

The National Cancer Institute's CTD2 Network maintains an Open-Access Data Portal that makes available raw data downloads from member Centers, including all raw sensitivity and enrichment data and other supporting information from the Broad related to this portal.

The Cancer Cell Line Encyclopedia provides public access to genomic data, analysis and visualization for about 1000 cell lines.

The Genomics of Drug Sensitivity in Cancer provides public access to data on the sensitivity of genomically characterized cancer cell lines to select compounds.

Project Achilles is a systematic effort aimed at identifying and cataloging genetic vulnerabilities across hundreds of genomically characterized cancer cell lines.