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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA209891-04
Application #
9953982
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Hughes, Shannon K
Project Start
2017-05-11
Project End
2022-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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