{"id":"https://openalex.org/W4403537767","doi":"https://doi.org/10.1016/j.esmoop.2024.103799","title":"54P Integrative omics workflow identifies credible druggable targets in high-grade serous cancer","display_name":"54P Integrative omics workflow identifies credible druggable targets in high-grade serous cancer","publication_year":2024,"publication_date":"2024-10-01","ids":{"openalex":"https://openalex.org/W4403537767","doi":"https://doi.org/10.1016/j.esmoop.2024.103799"},"language":"en","primary_location":{"id":"doi:10.1016/j.esmoop.2024.103799","doi":"https://doi.org/10.1016/j.esmoop.2024.103799","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.esmoop.2024.103799","pdf_url":"https://www.esmoopen.com/article/S2059-7029(24)01569-2/pdf","source":{"id":"https://openalex.org/S4210217024","display_name":"ESMO Open","issn_l":"2059-7029","issn":["2059-7029"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-40","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"ESMO Open","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.esmoopen.com/article/S2059-7029(24)01569-2/pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5081088648","display_name":"T.A. Muranen","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I133731052","display_name":"University of Helsinki","ror":"https://ror.org/040af2s02","country_code":"FI","type":"education","lineage":["https://openalex.org/I133731052"]}],"countries":["FI"],"is_corresponding":false,"raw_author_name":"T.A. Muranen","raw_affiliation_strings":["Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland","institution_ids":["https://openalex.org/I133731052"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5126181842","display_name":"Andreas Hainari","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I133731052","display_name":"University of Helsinki","ror":"https://ror.org/040af2s02","country_code":"FI","type":"education","lineage":["https://openalex.org/I133731052"]}],"countries":["FI"],"is_corresponding":false,"raw_author_name":"A. Hainari","raw_affiliation_strings":["Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland","institution_ids":["https://openalex.org/I133731052"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075672043","display_name":"Jaana Oikkonen","orcid":"https://orcid.org/0000-0002-1063-2736","observed_orcids":["https://orcid.org/0000-0002-1063-2736"]},"institutions":[{"id":"https://openalex.org/I133731052","display_name":"University of Helsinki","ror":"https://ror.org/040af2s02","country_code":"FI","type":"education","lineage":["https://openalex.org/I133731052"]}],"countries":["FI"],"is_corresponding":false,"raw_author_name":"J. Oikkonen","raw_affiliation_strings":["Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland","institution_ids":["https://openalex.org/I133731052"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006337168","display_name":"Daria Afenteva","orcid":"https://orcid.org/0009-0000-9596-2832","observed_orcids":["https://orcid.org/0009-0000-9596-2832"]},"institutions":[{"id":"https://openalex.org/I133731052","display_name":"University of Helsinki","ror":"https://ror.org/040af2s02","country_code":"FI","type":"education","lineage":["https://openalex.org/I133731052"]}],"countries":["FI"],"is_corresponding":false,"raw_author_name":"D. Afenteva","raw_affiliation_strings":["Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland","institution_ids":["https://openalex.org/I133731052"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013696600","display_name":"Wojciech Senkowski","orcid":"https://orcid.org/0000-0001-8120-1944","observed_orcids":["https://orcid.org/0000-0001-8120-1944"]},"institutions":[{"id":"https://openalex.org/I124055696","display_name":"University of Copenhagen","ror":"https://ror.org/035b05819","country_code":"DK","type":"education","lineage":["https://openalex.org/I124055696"]}],"countries":["DK"],"is_corresponding":false,"raw_author_name":"W. Senkowski","raw_affiliation_strings":["Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark","institution_ids":["https://openalex.org/I124055696"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5067760174","display_name":"Krister Wennerberg","orcid":"https://orcid.org/0000-0002-1352-4220","observed_orcids":["https://orcid.org/0000-0002-1352-4220"]},"institutions":[{"id":"https://openalex.org/I124055696","display_name":"University of Copenhagen","ror":"https://ror.org/035b05819","country_code":"DK","type":"education","lineage":["https://openalex.org/I124055696"]}],"countries":["DK"],"is_corresponding":false,"raw_author_name":"K. Wennerberg","raw_affiliation_strings":["Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark","institution_ids":["https://openalex.org/I124055696"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044104350","display_name":"Johanna Hynninen","orcid":"https://orcid.org/0000-0002-0854-7225","observed_orcids":["https://orcid.org/0000-0002-0854-7225"]},"institutions":[{"id":"https://openalex.org/I2801970007","display_name":"Turku University Hospital","ror":"https://ror.org/05dbzj528","country_code":"FI","type":"healthcare","lineage":["https://openalex.org/I2801970007","https://openalex.org/I4210127022"]}],"countries":["FI"],"is_corresponding":false,"raw_author_name":"J. Hynninen","raw_affiliation_strings":["Gynecology Department, Turku University Hospital TYKS, Turku, Finland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Gynecology Department, Turku University Hospital TYKS, Turku, Finland","institution_ids":["https://openalex.org/I2801970007"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5033102814","display_name":"Sampsa Hautaniemi","orcid":"https://orcid.org/0000-0002-7749-2694","observed_orcids":["https://orcid.org/0000-0002-7749-2694"]},"institutions":[{"id":"https://openalex.org/I133731052","display_name":"University of Helsinki","ror":"https://ror.org/040af2s02","country_code":"FI","type":"education","lineage":["https://openalex.org/I133731052"]}],"countries":["FI"],"is_corresponding":false,"raw_author_name":"S. Hautaniemi","raw_affiliation_strings":["Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research Program in Systems Oncology, University of Helsinki - Faculty of Medicine, Helsinki, Finland","institution_ids":["https://openalex.org/I133731052"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":3730,"currency":"USD","value_usd":3730},"apc_paid":{"value":3730,"currency":"USD","value_usd":3730},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.23860175,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"9","issue":null,"first_page":"103799","last_page":"103799"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10550","display_name":"Ovarian cancer diagnosis and treatment","score":0.9839000105857849,"subfield":{"id":"https://openalex.org/subfields/2743","display_name":"Reproductive Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10550","display_name":"Ovarian cancer diagnosis and treatment","score":0.9839000105857849,"subfield":{"id":"https://openalex.org/subfields/2743","display_name":"Reproductive Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.00839999970048666,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10769","display_name":"BRCA gene mutations in cancer","score":0.003700000001117587,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/high-grade-serous-carcinoma","display_name":"high-grade serous carcinoma","score":0.9169999957084656},{"id":"https://openalex.org/keywords/ovarian-cancer","display_name":"ovarian cancer","score":0.9879999756813049},{"id":"https://openalex.org/keywords/druggable-targets","display_name":"druggable targets","score":0.8690000176429749},{"id":"https://openalex.org/keywords/copy-number-alterations","display_name":"copy number alterations","score":0.7429999709129333},{"id":"https://openalex.org/keywords/driver-mutations","display_name":"driver mutations","score":0.7099999785423279},{"id":"https://openalex.org/keywords/multi-omics-integration","display_name":"multi-omics integration","score":0.6850000023841858},{"id":"https://openalex.org/keywords/nf1-loss","display_name":"NF1 loss","score":0.8149999976158142},{"id":"https://openalex.org/keywords/mapk-signaling","display_name":"MAPK signaling","score":0.9110000133514404},{"id":"https://openalex.org/keywords/pi3k-signaling","display_name":"PI3K signaling","score":0.9900000095367432},{"id":"https://openalex.org/keywords/homologous-recombination-deficiency","display_name":"homologous recombination deficiency","score":0.8870000243186951},{"id":"https://openalex.org/keywords/patient-derived-organoids","display_name":"patient-derived organoids","score":0.9350000023841858},{"id":"https://openalex.org/keywords/carboplatin","display_name":"carboplatin","score":0.6620000004768372},{"id":"https://openalex.org/keywords/rmc-7977","display_name":"RMC-7977","score":0.9869999885559082},{"id":"https://openalex.org/keywords/pan-ras-inhibitors","display_name":"pan-RAS inhibitors","score":0.859000027179718},{"id":"https://openalex.org/keywords/drug-sensitivity","display_name":"drug sensitivity","score":0.6600000262260437}],"concepts":[{"id":"https://openalex.org/C10679952","wikidata":"https://www.wikidata.org/wiki/Q5308937","display_name":"Druggability","level":3,"score":0.8518375158309937},{"id":"https://openalex.org/C177212765","wikidata":"https://www.wikidata.org/wiki/Q627335","display_name":"Workflow","level":2,"score":0.7141026258468628},{"id":"https://openalex.org/C157585117","wikidata":"https://www.wikidata.org/wiki/Q158666","display_name":"Omics","level":2,"score":0.6626007556915283},{"id":"https://openalex.org/C2993684365","wikidata":"https://www.wikidata.org/wiki/Q172341","display_name":"Serous ovarian cancer","level":4,"score":0.5741665363311768},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4349895417690277},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3635217845439911},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.35826975107192993},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.3534092307090759},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.319283664226532},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.31317687034606934},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.22181737422943115},{"id":"https://openalex.org/C77088390","wikidata":"https://www.wikidata.org/wiki/Q8513","display_name":"Database","level":1,"score":0.11273366212844849},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.09719341993331909},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.09043747186660767},{"id":"https://openalex.org/C2780427987","wikidata":"https://www.wikidata.org/wiki/Q172341","display_name":"Ovarian cancer","level":3,"score":0.07960367202758789}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1016/j.esmoop.2024.103799","doi":"https://doi.org/10.1016/j.esmoop.2024.103799","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.esmoop.2024.103799","pdf_url":"https://www.esmoopen.com/article/S2059-7029(24)01569-2/pdf","source":{"id":"https://openalex.org/S4210217024","display_name":"ESMO Open","issn_l":"2059-7029","issn":["2059-7029"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-40","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"ESMO Open","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.1016/j.esmoop.2024.103799","doi":"https://doi.org/10.1016/j.esmoop.2024.103799","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.esmoop.2024.103799","pdf_url":"https://www.esmoopen.com/article/S2059-7029(24)01569-2/pdf","source":{"id":"https://openalex.org/S4210217024","display_name":"ESMO Open","issn_l":"2059-7029","issn":["2059-7029"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-40","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"ESMO Open","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.98580002784729,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4403537767.pdf","grobid_xml":"https://content.openalex.org/works/W4403537767.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7167270518","https://openalex.org/W6889034982","https://openalex.org/W4414710016","https://openalex.org/W6978219136","https://openalex.org/W4315977422","https://openalex.org/W7131732531","https://openalex.org/W7154569415","https://openalex.org/W4321372870","https://openalex.org/W2331222999","https://openalex.org/W2781335926"],"abstract_inverted_index":{"Background:":[0],"The":[1,66,169],"ovarian":[2],"high-grade":[3],"serous":[4],"carcinoma":[5],"(HGSC)":[6],"lags":[7],"in":[8,27,152,166,214,235,246,301,311],"the":[9,24,34,84,92,117,128,153,175,219,223,239,260,263,292,295,308],"exploitation":[10],"of":[11,18,77,114,190,205,209,218,259,286,294],"personalized":[12],"biological":[13],"therapies,":[14],"while":[15],"targeted":[16,257],"inhibition":[17],"cancer":[19,75,149,224],"driver":[20,43,64,304],"events":[21,118,141],"has":[22],"improved":[23],"patient":[25],"care":[26],"other":[28],"solid":[29],"tumor":[30],"types.This":[31],"ows":[32],"to":[33,40,50,58,83,159],"copynumber":[35],"driven":[36],"HGSC":[37],"pathogenesis,":[38],"leading":[39],"few":[41],"short":[42,97],"mutations.We":[44],"introduce":[45],"a":[46,137,249,270,278,287,312],"systematic":[47,279],"multi-omic":[48],"workflow":[49,68,283],"integrate":[51],"evidence":[52],"from":[53,73],"genomic":[54,297],"and":[55,62,87,104,106,122,124,134,146,156,177,183,188,280,298,306],"transcriptomic":[56,299],"data":[57,72],"identify":[59,160],"credible,":[60],"recurring,":[61],"targetable":[63],"events.Methods:":[65],"multi-omics":[67],"was":[69,212,267],"piloted":[70],"with":[71,80,144,255,273],"831":[74],"samples":[76],"290":[78],"patients":[79],"HGSC,":[81],"enrolled":[82],"ongoing":[85],"prospective":[86],"longitudinal":[88],"DECIDER":[89],"study":[90],"at":[91],"Turku":[93],"University":[94],"Hospital.We":[95],"assembled":[96],"mutations,":[98],"copy":[99,288],"number":[100],"changes,":[101],"large":[102],"indels,":[103],"translocations,":[105],"classified":[107],"them":[108],"as":[109,136],"potential":[110],"loss":[111,182],"or":[112,195,198],"gain":[113],"function.We":[115],"evaluated":[116],"by":[119,193,222],"their":[120],"heterogeneity":[121],"direct":[123],"downstream":[125],"consequence":[126],"on":[127],"RNA":[129],"level,":[130],"using":[131],"prediction":[132],"algorithms":[133],"databases":[135],"support.The":[138],"credible":[139],"oncogenic":[140,172],"were":[142,233,242],"overlayed":[143],"targets":[145,155],"biomarkers":[147],"for":[148,164,253,269,284],"medicines":[150],"listed":[151],"Open":[154],"OncoKB":[157],"databases,":[158],"promising":[161],"treatment":[162],"modalities":[163],"testing":[165],"patient-derived":[167,271,313],"organoids.Results:":[168],"most":[170],"frequent":[171],"aberrations":[173,211,220,305],"affecting":[174,186,202],"MAPK":[176,261],"PI3K":[178],"patways":[179],"included":[180],"NF1":[181,231,274],"AKT2":[184,240],"amplification,":[185],"19%":[187],"9%":[189],"cases,":[191],"followed":[192],"PTK2":[194],"KRAS":[196],"amplifications":[197,241],"PTEN":[199],"loss,":[200],"each":[201],"about":[203],"5%":[204],"cases.At":[206],"least":[207],"one":[208],"these":[210],"detected":[213,243],"47%":[215],"cancers.The":[216],"frequency":[217],"varied":[221],"homologous":[225],"recombination":[226],"(HR)":[227],"status,":[228],"so":[229],"that":[230],"losses":[232],"enriched":[234],"HR-deficient":[236],"cancers,":[237],"but":[238],"almost":[244],"exclusively":[245],"HR-proficient":[247],"cancers.In":[248],"drug":[250],"sensitization":[251],"screen":[252],"carboplatin":[254],"different":[256],"inhibitors":[258],"pathway,":[262],"pan-RAS":[264],"inhibitor":[265],"RMC-7977":[266],"effective":[268],"organoid":[272],"loss.Conclusions:":[275],"We":[276],"developed":[277],"comprehensive":[281],"omics":[282],"analysis":[285,300],"number-driven":[289],"cancer.We":[290],"demonstrated":[291],"utility":[293],"integrated":[296],"identifying":[302],"druggable":[303],"validated":[307],"predicted":[309],"sensitivity":[310],"organoid.Clinical":[314],"trial":[315],"identification:":[316],"NCT04846933.":[317]},"counts_by_year":[],"updated_date":"2026-10-12T09:40:04.860316","created_date":"2024-10-19T00:00:00"}