title: Predicting selective drug targets in cancer through metabolic networks.
abstract: The interest in studying metabolic alterations in cancer and their potential role as novel targets for therapy has been rejuvenated in recent years. Here, we report the development of the first genome-scale network model of cancer metabolism, validated by correctly identifying genes essential for cellular proliferation in cancer cell lines. The model predicts 52 cytostatic drug targets, of which 40% are targeted by known, approved or experimental anticancer drugs, and the rest are new. It further predicts combinations of synthetic lethal drug targets, whose synergy is validated using available drug efficacy and gene expression measurements across the NCI-60 cancer cell line collection. Finally, potential selective treatments for specific cancers that depend on cancer type-specific downregulation of gene expression and somatic mutations are compiled.
authors.affiliation: The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Folger
authors.forename: Livnat
authors.initials: L
authors.lastname: Jerby
authors.forename: Christian
authors.initials: C
authors.lastname: Frezza
authors.forename: Eyal
authors.initials: E
authors.lastname: Gottlieb
authors.forename: Eytan
authors.initials: E
authors.lastname: Ruppin
authors.forename: Tomer
authors.initials: T
authors.lastname: Shlomi
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019295:Computational Biology; D054697:Cytostatic Agents / Q000737:chemistry*; D015536:Down-Regulation; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D054697:Cytostatic Agents; D034741:RNA, Small Interfering