An Interactive Resource to Identify Cancer Genetic and Lineage Dependencies Targeted by Small Molecules

被引：566

作者：

Basu, Amrita ^{[1
]}

Bodycombe, Nicole E. ^{[1
]}

Cheah, Jaime H. ^{[1
]}

Price, Edmund V. ^{[1
]}

Liu, Ke ^{[1
]}

Schaefer, Giannina I. ^{[1
]}

Ebright, Richard Y. ^{[1
]}

Stewart, Michelle L. ^{[1
]}

Ito, Daisuke ^{[1
]}

Wang, Stephanie ^{[1
]}

Bracha, Abigail L. ^{[1
]}

Liefeld, Ted ^{[1
]}

Wawer, Mathias ^{[1
]}

Gilbert, Joshua C. ^{[1
]}

Wilson, Andrew J. ^{[2
]}

Stransky, Nicolas ^{[1
]}

Kryukov, Gregory V. ^{[1
]}

Dancik, Vlado ^{[1
]}

Barretina, Jordi ^{[1
]}

Garraway, Levi A. ^{[1
]}

Hon, C. Suk-Yee ^{[1
]}

Munoz, Benito ^{[1
]}

Bittker, Joshua A. ^{[1
]}

Stockwell, Brent R. ^{[3
]}

Khabele, Dineo ^{[2
]}

Stern, Andrew M. ^{[1
]}

Clemons, Paul A. ^{[1
]}

Shamji, Alykhan F. ^{[1
]}

Schreiber, Stuart L. ^{[1
]}

机构：

[1] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[2] Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA

[3] Columbia Univ, New York, NY 10027 USA

来源：

CELL | 2013年 / 154卷 / 05期

关键词：

INHIBITION; IDENTIFICATION; SENSITIVITY; RESISTANCE; THERAPIES; SURVIVAL; PATHWAY; KINASE; CELLS; BCL-2;

D O I：

10.1016/j.cell.2013.08.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 beta-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.

引用

页码：1151 / 1161

页数：11

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