An Interactive Resource to Identify Cancer Genetic and Lineage Dependencies Targeted by Small Molecules
Cet article présente un portail de données qui, pour plus de 200 lignées cellulaires cancéreuses, dresse un catalogue de leur sensibilité à 345 petites molécules
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.
"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
The Cancer Therapeutics Response Portal catalogs the sensitivity of more than 200 cancer cell lines to specific small molecules. This resource should accelerate the development of individualized therapies tailored to specific cancers and patients.
Cell , résumé, 2012