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Project DRIVE - A compendium of cancer dependencies and synthetic lethal relationships uncovered by large scale, deep RNAi screening

Mcdonald Iii, Earl and De Weck, Antoine and Kauffmann, Audrey and Schmelzle, Tobias and Golji, Javad (2017) Project DRIVE - A compendium of cancer dependencies and synthetic lethal relationships uncovered by large scale, deep RNAi screening. Cell, 170 (3). pp. 577-592.

Abstract

The elucidation of the mutational landscape of human cancer has made rapid progress accompanied by the development of therapeutics targeting selected 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 further the identification of vulnerabilities relevant to specific genetic and lineage subtypes of cancer 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 the 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 that recapitulate 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.

Item Type: Article
Date Deposited: 15 Aug 2017 00:45
Last Modified: 15 Aug 2017 00:45
URI: https://oak.novartis.com/id/eprint/31854

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