THECANCERCELLMAPINITIATIVE: ANATIONALRESEARCHCENTERFORCANCERSYSTEMSBIOLOGY OVERALLSUMMARY TheCancerGenomeAtlasandsisterprojectshavenowcompletedanalysisofover10,000tumorgenomes, providing a catalog of the gene mutations, copy number variants and other genetic alterations that cause cancer.Inmanycasesitremainsunclear,however,whicharethekeydrivermutationsordependenciesina givencancerandhowtheseinfluencepathogenesisandresponsetotherapy.Althoughtumorsofsimilartypes andclinicaloutcomescanhavepatternsofmutationsthatarestrikinglydifferent,itisbecomingapparentthat these mutations recurrently hijack the same hallmark molecular pathways and networks. For this reason, cancer research and treatment is increasingly dependent on knowledge of biological networks of multiple types, including physical interactions among proteins and syntheticlethal and epistatic interactions among genes. Here we seek support for a new effort, The Cancer Cell Map Initiative (CCMI), aimed at comprehensivelydetailingthesecomplexinteractionsamongcancergenesandproteinsandhowtheydiffer between diseased and healthy states. The CCMI is a multicampus initiative of the University of California, centeredatUCSanFranciscoandUCSanDiego,whichleveragesadvancednetworkmapping,computational analysisandcancerresearchplatformsdevelopedbymultipleCCMIinvestigatorsoverthepastdecade.Thus primed,theseplatformswillbeturnedtoefficientlygenerate,assembleandanalyzecancermolecularnetworks withaviewtowardspathwayandnetworkbasedpersonalizedtherapy.Specifically,overthenextfiveyears theCCMIwillseektocatalyzemajorphasetransitionsincancerresearchandtherapyby(1)Comprehensively mapping the networks of physical interactions among cancer proteins, revealing the protein complexes and higherorder molecular units under selection in cancer? (2) Mapping the parallel networks of syntheticlethal andepistaticinteractionsamongcancergenes,revealingthefunctionallogicofcancer?(3)Establishingthe robust computational methodology, enduser software, and databases for assembly and use of cancer cell networkmapsinbothbasicandclinicalmodalities?(4)Buildingacriticalmassofleadingcancerinvestigators worldwide to expand CCMI into a global coordinated partnership? and (5) Training the current and nextgenerationofscientistsinNetworkBiologyanditsapplicationstocancerresearch.
THECANCERCELLMAPINITIATIVE: ANATIONALRESEARCHCENTERFORCANCERSYSTEMSBIOLOGY OVERALLNARRATIVE Although much attention has been devoted to mapping the tumor genome, understanding cancer involves morethancataloguingitscomponentgenes.Itiscriticaltounderstandthemanyinteractionsbetweenthese genes and the corresponding proteins, and how these complex networks gives rise to tumor initiation, progression and metastasis. The Cancer Cell Map Initiative will apply systematic approaches to comprehensivelymapthemolecularnetworksthatunderliecancerandwillusethesemapsasakeyresource forprecisionmedicine.
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