Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening

被引：468

作者：

McDonald, E. Robert, III ^{[1
,2
,3
]}

de Weck, Antoine ^{[1
,2
,3
]}

Schlabach, Michael R. ^{[1
,2
,3
]}

Billy, Eric ^{[1
,2
,3
]}

Mavrakis, Konstantinos J. ^{[1
,2
,3
]}

Hoffman, Gregory R. ^{[1
,2
,3
]}

Belur, Dhiren ^{[1
,2
,3
]}

Castelletti, Deborah ^{[1
,2
,3
]}

Frias, Elizabeth ^{[1
,2
,3
]}

Gampa, Kalyani ^{[1
,2
,3
]}

Golji, Javad ^{[1
,2
,3
]}

Kao, Iris ^{[1
,2
,3
]}

Li, Li ^{[1
,2
,3
]}

Megel, Philippe ^{[1
,2
,3
]}

Perkins, Thomas A. ^{[1
,2
,3
]}

Ramadan, Nadire ^{[1
,2
,3
]}

Ruddy, David A. ^{[1
,2
,3
]}

Silver, Serena J. ^{[1
,2
,3
]}

Sovath, Sosathya ^{[1
,2
,3
]}

Stump, Mark ^{[1
,2
,3
]}

Weber, Odile ^{[1
,2
,3
]}

Widmer, Roland ^{[1
,2
,3
]}

Yu, Jianjun ^{[1
,2
,3
]}

Yu, Kristine ^{[1
,2
,3
]}

Yue, Yingzi ^{[1
,2
,3
]}

Abramowski, Dorothee ^{[1
,2
,3
]}

Ackley, Elizabeth ^{[1
,2
,3
]}

Barrett, Rosemary ^{[1
,2
,3
]}

Berger, Joel ^{[1
,2
,3
]}

Bernard, Julie L. ^{[1
,2
,3
]}

Billig, Rebecca ^{[1
,2
,3
]}

Brachmann, Saskia M. ^{[1
,2
,3
]}

Buxton, Frank ^{[1
,2
,3
]}

Caothien, Roger ^{[1
,2
,3
]}

Caushi, Justina X. ^{[1
,2
,3
]}

Chung, Franklin S. ^{[1
,2
,3
]}

Cortes-Cros, Marta ^{[1
,2
,3
]}

debeaumont, Rosalie S. ^{[1
,2
,3
]}

Delaunay, Clara ^{[1
,2
,3
]}

Desplat, Aurore ^{[1
,2
,3
]}

Duong, William ^{[1
,2
,3
]}

Dwoske, Donald A. ^{[1
,2
,3
]}

Eldridge, Richard S. ^{[1
,2
,3
]}

Farsidjani, Ali ^{[1
,2
,3
]}

Feng, Fei ^{[1
,2
,3
]}

Feng, JiaJia ^{[1
,2
,3
]}

Flemming, Daisy ^{[1
,2
,3
]}

Forrester, William ^{[1
,2
,3
]}

Galli, Giorgio G. ^{[1
,2
,3
]}

Gao, Zhenhai ^{[1
,2
,3
]}

机构：

[1] Novartis Inst Biomed Res, Oncol Dis Area, CH-4002 Basel, Switzerland

[2] Novartis Inst Biomed Res, Oncol Dis Area, Cambridge, MA 02139 USA

[3] Novartis Inst Biomed Res, Oncol Dis Area, Emeryville, CA 94608 USA

来源：

CELL | 2017年 / 170卷 / 03期

关键词：

C-RAF; GENE; BREAST; VULNERABILITIES; INHIBITOR; MUTATIONS; PHENOTYPE; ADDICTION; PROTEINS; DELETION;

D O I：

10.1016/j.cell.2017.07.005

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：

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer.

引用

页码：577 / +

页数：26

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