< Back to Publications
An interactive resource to identify cancer genetic and lineage dependencies targeted by small molecules.
|Publication Type||Journal Article|
|Authors||Basu, A., Bodycombe NE, Cheah JH, Price EV, Liu K., Schaefer GI, Ebright RY, Stewart ML, Ito D., Wang S., Bracha AL, Liefeld T., Wawer M., Gilbert JC, Wilson AJ, Stransky N., Kryukov GV, Dancik V., Barretina J., Garraway LA, Hon CS, Munoz B., Bittker JA, Stockwell BR, Khabele D., Stern AM, Clemons PA, Shamji AF, and Schreiber SL|
|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|
|Date Published (YYYY/MM/DD)||2013/08/29|