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Cell DOI:10.1016/j.cell.2013.08.003

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

Publication TypeJournal Article
Year of Publication2013
AuthorsBasu, 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, Dančík, V, Barretina, J, Garraway, LA, C Hon, S-Y, Munoz, B, Bittker, JA, Stockwell, BR, Khabele, D, Stern, AM, Clemons, PA, Shamji, AF, Schreiber, SL
JournalCell
Volume154
Issue5
Pages1151-61
Date Published2013 Aug 29
ISSN1097-4172
KeywordsAntineoplastic Agents, Cell Line, Tumor, Databases, Pharmaceutical, Drug Discovery, Humans, Neoplasms
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0092-8674(13)00960-4
DOI10.1016/j.cell.2013.08.003
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23993102?dopt=Abstract

Alternate JournalCell
PubMed ID23993102
PubMed Central IDPMC3954635
Grant ListRC2 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
U54 CA112962 / CA / NCI NIH HHS / United States