{"id":"https://openalex.org/W4367603582","doi":"https://doi.org/10.1158/1557-3125.ras23-ia06","title":"Abstract IA06: Targeting the ERK-MYC signaling network for the treatment of KRAS-mutant cancers","display_name":"Abstract IA06: Targeting the ERK-MYC signaling network for the treatment of KRAS-mutant cancers","publication_year":2023,"publication_date":"2023-05-01","ids":{"openalex":"https://openalex.org/W4367603582","doi":"https://doi.org/10.1158/1557-3125.ras23-ia06"},"language":"en","primary_location":{"id":"doi:10.1158/1557-3125.ras23-ia06","doi":"https://doi.org/10.1158/1557-3125.ras23-ia06","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1557-3125.ras23-ia06","pdf_url":null,"source":{"id":"https://openalex.org/S192067876","display_name":"Molecular Cancer Research","issn_l":"1541-7786","issn":["1541-7786","1557-3125"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Cancer Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5064063895","display_name":"Channing J. Der","orcid":"https://orcid.org/0000-0002-7751-2747","observed_orcids":["https://orcid.org/0000-0002-7751-2747"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Channing J. Der","raw_affiliation_strings":["1University of North Carolina at Chapel Hill, Chapel Hill, NC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of North Carolina at Chapel Hill, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5064063895"],"corresponding_institution_ids":["https://openalex.org/I114027177"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"21","issue":"5_Supplement","first_page":"IA06","last_page":"IA06"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.676800012588501,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.676800012588501,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.24050000309944153,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"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/T11533","display_name":"Melanoma and MAPK Pathways","score":0.02459999918937683,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"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/mek-erk-signaling","display_name":"MEK/ERK signaling","score":0.7570000290870667},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.527999997138977},{"id":"https://openalex.org/keywords/phosphoproteome","display_name":"phosphoproteome","score":0.7080000042915344},{"id":"https://openalex.org/keywords/kinome","display_name":"kinome","score":0.6840000152587891},{"id":"https://openalex.org/keywords/rho-gtpases","display_name":"Rho GTPases","score":0.7760000228881836},{"id":"https://openalex.org/keywords/cell-cycle-progression","display_name":"cell cycle progression","score":0.6370000243186951}],"concepts":[{"id":"https://openalex.org/C2781187634","wikidata":"https://www.wikidata.org/wiki/Q20969980","display_name":"KRAS","level":4,"score":0.9791951179504395},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.7116059064865112},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6789286732673645},{"id":"https://openalex.org/C54174078","wikidata":"https://www.wikidata.org/wiki/Q3197188","display_name":"Kinome","level":3,"score":0.5032636523246765},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5000653266906738},{"id":"https://openalex.org/C2781249067","wikidata":"https://www.wikidata.org/wiki/Q17142288","display_name":"MEK inhibitor","level":4,"score":0.4665977954864502},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.42580878734588623},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.42440688610076904},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.41319411993026733},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.3496667742729187},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.3134782910346985},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.23808073997497559},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.15119829773902893},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.1509144902229309}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1557-3125.ras23-ia06","doi":"https://doi.org/10.1158/1557-3125.ras23-ia06","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1557-3125.ras23-ia06","pdf_url":null,"source":{"id":"https://openalex.org/S192067876","display_name":"Molecular Cancer Research","issn_l":"1541-7786","issn":["1541-7786","1557-3125"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9537000060081482,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4210435720","https://openalex.org/W4367602905","https://openalex.org/W2562074085","https://openalex.org/W2250059052","https://openalex.org/W4396850105","https://openalex.org/W7133792990","https://openalex.org/W4399394643","https://openalex.org/W7154478591","https://openalex.org/W7165479455","https://openalex.org/W4362593843"],"abstract_inverted_index":{"Abstract":[0],"KRAS":[1,28,39,51,64,85,101,205],"is":[2,121],"mutationally":[3],"activated":[4],"in":[5,53,70,138,184],"95%":[6],"of":[7,16,24,26,35,38,50,61,83,90,100,108,114,134,146,160,216,233,238,299,305],"pancreatic":[8],"ductal":[9],"adenocarcinomas":[10],"(PDAC)":[11],"and":[12,68,75,182,194,219,250,266,279],"essential":[13],"for":[14,40,296],"maintenance":[15],"PDAC":[17,41,139,170,284],"tumorigenic":[18],"growth.":[19,171,285],"The":[20],"recent":[21,131],"clinical":[22,132],"evaluation":[23,133],"inhibitors":[25,60,96],"one":[27,105],"mutant":[29,45],"(KRASG12C)":[30],"supports":[31,168],"the":[32,62,81,144,161,175,202,245,292,297,306],"therapeutic":[33,148],"value":[34],"direct":[36,59,84,135],"targeting":[37],"treatment.":[42],"However,":[43,129],"this":[44,147],"comprises":[46,104],"less":[47],"than":[48],"2%":[49],"mutations":[52,65],"PDAC.":[54,71,186],"Therefore,":[55],"we":[56,173,242],"have":[57],"evaluated":[58],"predominant":[63],"(G12D,":[66],"G12V":[67],"G12R)":[69],"Additionally,":[72],"both":[73],"innate":[74],"treatment-associated":[76],"resistance":[77,125],"mechanisms":[78,163],"will":[79],"limit":[80],"effectiveness":[82,145],"inhibitors.":[86,128],"Genomic":[87],"sequencing":[88],"analyses":[89,261],"patients":[91],"who":[92],"relapsed":[93],"on":[94,213],"KRASG12C":[95],"suggest":[97],"that":[98,112,141,198,254,271],"reactivation":[99],"effector":[102],"signaling":[103,167,235,269,294],"major":[106,231],"mechanism":[107],"resistance.":[109],"We":[110,187,208],"determined":[111,174,244],"activation":[113,119,237],"MEK-ERK":[115],"but":[116],"not":[117,223],"AKT":[118],"alone":[120],"sufficient":[122],"to":[123,126,155,281],"drive":[124],"KRASG12C/D":[127],"our":[130,153],"ERK":[136,166,234],"inhibition":[137],"found":[140],"toxicity":[142],"limited":[143],"approach.":[149],"These":[150],"observations":[151],"prompted":[152],"studies":[154],"complete":[156],"a":[157,230,263],"system-wide":[158],"determination":[159],"molecular":[162],"by":[164],"which":[165,217],"KRAS-dependent":[169,189,193,283],"First,":[172],"KRAS-ERK":[176],"regulated":[177],"transcriptome,":[178],"kinome,":[179],"total":[180],"proteome":[181],"phosphoproteome":[183],"KRAS-mutant":[185,300],"identified":[188,209],"gene":[190,206,240],"signature":[191],"(677":[192],"1,051":[195],"KRAS-suppressed":[196],"genes)":[197,253],"diverged":[199],"significantly":[200],"from":[201],"classical":[203],"Hallmark":[204],"signature.":[207],"5,117":[210],"ERK-dependent":[211],"phosphosites":[212],"2,252":[214],"proteins,":[215],"88%":[218],"67%,":[220],"respectively,":[221],"were":[222],"previously":[224],"associated":[225],"with":[226],"ERK.":[227],"Second,":[228],"since":[229],"consequence":[232],"involves":[236],"MYC-regulated":[239],"transcription,":[241],"also":[243],"MYC-dependent":[246,249],"transcriptome":[247],"(2,086":[248],"2,403":[251],"MYC-suppressed":[252],"include":[255],"80":[256],"protein":[257],"kinases.":[258],"Together,":[259],"these":[260],"define":[262],"highly":[264],"complex":[265],"dynamic":[267],"ERK-regulated":[268],"network":[270,295],"deregulates":[272],"cell":[273],"cycle":[274],"progression,":[275],"RHO":[276],"GTPase":[277],"function":[278],"metabolism":[280],"support":[282],"Citation":[286],"Format:":[287],"Channing":[288],"J.":[289],"Der.":[290],"Targeting":[291,310],"ERK-MYC":[293],"treatment":[298],"cancers":[301],"[abstract].":[302],"In:":[303],"Proceedings":[304],"AACR":[307],"Special":[308],"Conference:":[309],"RAS;":[311],"2023":[312],"Mar":[313],"5-8;":[314],"Philadelphia,":[315],"PA.":[316],"Philadelphia":[317],"(PA):":[318],"AACR;":[319],"Mol":[320],"Cancer":[321],"Res":[322],"2023;21(5_Suppl):Abstract":[323],"nr":[324],"IA06.":[325]},"counts_by_year":[],"updated_date":"2026-07-14T23:27:15.235271","created_date":"2023-05-02T00:00:00"}
