{"id":"https://openalex.org/W4282983007","doi":"https://doi.org/10.1158/1538-7445.am2022-1102","title":"Abstract 1102: Fyn and Src cooperate with ERBB family to drive resistance to crizotinib in ROS1+ and ALK+ NSCLC","display_name":"Abstract 1102: Fyn and Src cooperate with ERBB family to drive resistance to crizotinib in ROS1+ and ALK+ NSCLC","publication_year":2022,"publication_date":"2022-06-15","ids":{"openalex":"https://openalex.org/W4282983007","doi":"https://doi.org/10.1158/1538-7445.am2022-1102"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2022-1102","doi":"https://doi.org/10.1158/1538-7445.am2022-1102","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2022-1102","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","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":"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/A5076891434","display_name":"Logan C. Tyler","orcid":"https://orcid.org/0000-0002-4446-2253","observed_orcids":["https://orcid.org/0000-0002-4446-2253"]},"institutions":[{"id":"https://openalex.org/I51713134","display_name":"University of Colorado Anschutz","ror":"https://ror.org/03wmf1y16","country_code":"US","type":"education","lineage":["https://openalex.org/I51713134"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Logan C. Tyler","raw_affiliation_strings":["1University of Colorado-Anschutz Medical Campus, Aurora, CO"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Colorado-Anschutz Medical Campus, Aurora, CO","institution_ids":["https://openalex.org/I51713134"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100442873","display_name":"Nan Chen","orcid":"https://orcid.org/0009-0007-4593-0972","observed_orcids":["https://orcid.org/0009-0007-4593-0972"]},"institutions":[{"id":"https://openalex.org/I51713134","display_name":"University of Colorado Anschutz","ror":"https://ror.org/03wmf1y16","country_code":"US","type":"education","lineage":["https://openalex.org/I51713134"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nan Chen","raw_affiliation_strings":["1University of Colorado-Anschutz Medical Campus, Aurora, CO"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Colorado-Anschutz Medical Campus, Aurora, CO","institution_ids":["https://openalex.org/I51713134"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100753119","display_name":"Anh Tuan Le","orcid":"https://orcid.org/0000-0003-4221-0914","observed_orcids":["https://orcid.org/0000-0003-4221-0914"]},"institutions":[{"id":"https://openalex.org/I51713134","display_name":"University of Colorado Anschutz","ror":"https://ror.org/03wmf1y16","country_code":"US","type":"education","lineage":["https://openalex.org/I51713134"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Anh T. Le","raw_affiliation_strings":["1University of Colorado-Anschutz Medical Campus, Aurora, CO"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Colorado-Anschutz Medical Campus, Aurora, CO","institution_ids":["https://openalex.org/I51713134"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047106094","display_name":"Hala Nijmeh","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I51713134","display_name":"University of Colorado Anschutz","ror":"https://ror.org/03wmf1y16","country_code":"US","type":"education","lineage":["https://openalex.org/I51713134"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hala Nijmeh","raw_affiliation_strings":["1University of Colorado-Anschutz Medical Campus, Aurora, CO"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Colorado-Anschutz Medical Campus, Aurora, CO","institution_ids":["https://openalex.org/I51713134"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5018117492","display_name":"Liming Bao","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I51713134","display_name":"University of Colorado Anschutz","ror":"https://ror.org/03wmf1y16","country_code":"US","type":"education","lineage":["https://openalex.org/I51713134"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Liming Bao","raw_affiliation_strings":["1University of Colorado-Anschutz Medical Campus, Aurora, CO"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Colorado-Anschutz Medical Campus, Aurora, CO","institution_ids":["https://openalex.org/I51713134"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5034705456","display_name":"Robert Charles Doebele","orcid":"https://orcid.org/0000-0001-6728-6857","observed_orcids":["https://orcid.org/0000-0001-6728-6857"]},"institutions":[{"id":"https://openalex.org/I51713134","display_name":"University of Colorado Anschutz","ror":"https://ror.org/03wmf1y16","country_code":"US","type":"education","lineage":["https://openalex.org/I51713134"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Robert C. Doebele","raw_affiliation_strings":["1University of Colorado-Anschutz Medical Campus, Aurora, CO"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Colorado-Anschutz Medical Campus, Aurora, CO","institution_ids":["https://openalex.org/I51713134"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I51713134"],"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":"82","issue":"12_Supplement","first_page":"1102","last_page":"1102"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10417","display_name":"Lung Cancer Treatments and Mutations","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory 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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory 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":0.0,"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/T12334","display_name":"Lung Cancer Research Studies","score":0.0,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/crizotinib-resistance","display_name":"crizotinib resistance","score":0.9330000281333923},{"id":"https://openalex.org/keywords/ros1-positive-non-small-cell-lung-cancer","display_name":"ROS1-positive non-small cell lung cancer","score":0.8309999704360962},{"id":"https://openalex.org/keywords/alk-positive-non-small-cell-lung-cancer","display_name":"ALK-positive non-small cell lung cancer","score":0.9879999756813049},{"id":"https://openalex.org/keywords/fyn","display_name":"Fyn","score":0.8799999952316284},{"id":"https://openalex.org/keywords/src-family-kinases","display_name":"Src family kinases","score":0.9829999804496765},{"id":"https://openalex.org/keywords/erbb-signaling-pathway","display_name":"ErbB signaling","score":0.7850000262260437},{"id":"https://openalex.org/keywords/afatinib","display_name":"afatinib","score":0.8569999933242798},{"id":"https://openalex.org/keywords/mapk-signaling","display_name":"MAPK signaling","score":0.9190000295639038},{"id":"https://openalex.org/keywords/akt-signaling","display_name":"Akt signaling","score":0.9369999766349792},{"id":"https://openalex.org/keywords/eml4-alk-fusion","display_name":"EML4-ALK fusion","score":0.7440000176429749},{"id":"https://openalex.org/keywords/acquired-drug-resistance","display_name":"acquired drug resistance","score":0.4519999921321869},{"id":"https://openalex.org/keywords/tyrosine-kinase-inhibitor-resistance","display_name":"tyrosine kinase inhibitor resistance","score":0.37400001287460327}],"concepts":[{"id":"https://openalex.org/C2779422266","wikidata":"https://www.wikidata.org/wiki/Q5186964","display_name":"Crizotinib","level":4,"score":0.883791446685791},{"id":"https://openalex.org/C2775999482","wikidata":"https://www.wikidata.org/wiki/Q18031208","display_name":"ROS1","level":4,"score":0.727308452129364},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.706214189529419},{"id":"https://openalex.org/C2780586478","wikidata":"https://www.wikidata.org/wiki/Q4688818","display_name":"Afatinib","level":5,"score":0.5772780179977417},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.5010232925415039},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4831816256046295},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.42514368891716003},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.38547632098197937},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.34149694442749023},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.32903286814689636},{"id":"https://openalex.org/C2778087573","wikidata":"https://www.wikidata.org/wiki/Q418369","display_name":"Erlotinib","level":4,"score":0.3034830093383789},{"id":"https://openalex.org/C2781182431","wikidata":"https://www.wikidata.org/wiki/Q356033","display_name":"Adenocarcinoma","level":3,"score":0.28954508900642395},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.2853472828865051},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.27702581882476807},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.16807368397712708},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.09156626462936401},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.06385311484336853},{"id":"https://openalex.org/C2776232967","wikidata":"https://www.wikidata.org/wiki/Q6743514","display_name":"Malignant pleural effusion","level":3,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2022-1102","doi":"https://doi.org/10.1158/1538-7445.am2022-1102","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2022-1102","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","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":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9391000270843506,"display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","score":0.7400000095367432,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W1972760716","https://openalex.org/W2466915283","https://openalex.org/W2036215231","https://openalex.org/W2481271931","https://openalex.org/W2048560132","https://openalex.org/W2042517260","https://openalex.org/W3119596134","https://openalex.org/W1608478751","https://openalex.org/W4200595334","https://openalex.org/W2991748382"],"abstract_inverted_index":{"Abstract":[0],"ALK/ROS1":[1,83,368,391,413],"TKIs":[2,29,129,303,411],"have":[3],"significantly":[4],"improved":[5,136],"outcomes":[6],"for":[7,248,456],"patients":[8,25,49],"with":[9,203,223,240,290,301,360,367,412,436],"ALK/ROS1+":[10],"lung":[11,71],"adenocarcinoma.":[12],"However,":[13],"drug":[14],"resistance":[15,46,58,79,275,388,441],"inevitably":[16],"develops,":[17],"leading":[18],"to":[19,27,59,76,81,90,124,253,276,288,309,354,364,389,439,442],"disease":[20],"progression.":[21],"Approximately":[22],"1/3":[23],"of":[24,45,139,148,180,194,210,215,219,244,293,299,314,319,379,386,397,408,452],"resistant":[26,307],"ROS1":[28,32],"demonstrate":[30],"on-target":[31],"kinase":[33,127,256],"domain":[34],"(KD)":[35],"mutations":[36],"(Dziadziuszko":[37],"et":[38],"al.":[39],"ESMO":[40],"2019),":[41],"but":[42],"the":[43,82,92,197,249,291,297,334,376,406,453],"mechanism":[44,352,385],"in":[47,130,165,231,236,267,358,393,401,444],"most":[48],"remains":[50],"unknown/poorly":[51],"characterized.":[52],"To":[53,371],"model":[54],"and":[55,64,97,108,151,155,175,182,186,213,296,321,324,327,433,446],"characterize":[56],"acquired":[57,78,387],"crizotinib,":[60],"we":[61,263,339],"used":[62,87],"ROS1+":[63,445],"ALK+":[65,447],"primary,":[66],"patient":[67],"tumor-derived":[68],"non-small":[69],"cell":[70,74,105],"cancer":[72],"(NSCLC)":[73],"lines":[75],"generate":[77],"models":[80],"inhibitor":[84],"crizotinib.":[85,310,370],"We":[86],"several":[88],"techniques":[89],"probe":[91],"mechanisms":[93],"driving":[94,273],"resistance:":[95],"DNA":[96],"RNA":[98,144,176,312],"sequencing":[99],"(seq),":[100],"fluorescence":[101],"in-situ":[102],"hybridization":[103],"(FISH),":[104],"proliferation":[106,131],"assays,":[107,132],"western":[109,328],"blotting.":[110],"The":[111,395],"crizotinib-resistant":[112],"line":[113,251],"initially":[114],"driven":[115],"by":[116,137],"a":[117,204,245,351,384],"TPM3-ROS1":[118],"fusion":[119],"(CUTO28-CR)":[120],"displayed":[121],"exquisite":[122],"sensitivity":[123],"Src":[125,152,322,398,434],"family":[126,362,438],"(SFK)":[128],"which":[133],"was":[134],"modestly":[135],"addition":[138,214,292,298],"ERBB":[140,255,361,437],"TKI":[141,206,261,369,392],"afatinib.":[142],"Bulk":[143,311],"seq":[145,177,313],"revealed":[146,160,178,207,317],"upregulation":[147,179,193,318,332,396],"SFKs":[149],"Fyn":[150,195,320,344,400,432],"transcripts":[153,184],"(141-":[154],"2.31-fold,":[156],"respectively).":[157,188],"Interphase":[158],"FISH":[159],"modest":[161],"EGFR":[162,181],"gene":[163],"amplification":[164],"CUTO28-CR":[166,200,232],"cells":[167,201,233,266,284,308,316],"vs":[168,173],"parental":[169,237],"(EGFR:CEP7":[170],"ratio":[171],"2.1":[172],"1.0),":[174],"HER2":[183],"(1.79-":[185],"2.45-fold,":[187],"Western":[189],"blot":[190,329],"analysis":[191,330],"confirmed":[192,331],"at":[196,333],"protein":[198,335],"level.":[199,336],"treated":[202],"SFK":[205,294,302,342,410],"dose-dependent":[208],"deactivation":[209],"Akt":[211],"signaling,":[212,357],"afatinib":[216,271,300],"caused":[217],"inhibition":[218],"MAPK":[220,229],"signaling.":[221],"Stimulation":[222],"epidermal":[224],"growth":[225],"factor":[226],"(EGF)":[227],"enhanced":[228],"signaling":[230,280,382],"more":[234],"than":[235],"cells,":[238],"consistent":[239],"EGFR/HER2":[241],"dependence.":[242],"Because":[243],"noted":[246],"propensity":[247],"EML4-ALK":[250],"(H3122)":[252],"upregulate":[254],"activity":[257],"under":[258],"sustained":[259],"ALK":[260],"treatment,":[262],"maintained":[264],"these":[265,306],"low":[268],"dose":[269],"(25nM)":[270],"while":[272],"crizotinib":[274,289,443],"identify":[277],"additional":[278],"bypass":[279,356,381],"pathways.":[281],"These":[282],"H3122-CAR":[283,315],"were":[285],"partially":[286],"resensitized":[287,305],"TKIs,":[295],"further":[304],"(2.64-":[323],"3.63-fold,":[325],"respectively),":[326],"In":[337],"conclusion,":[338],"demonstrated":[340],"increased":[341],"(particularly":[343],"and/or":[345,348,399],"Src)":[346],"expression":[347],"activation":[349],"is":[350,375],"utilized":[353],"drive":[355,440],"cooperation":[359],"kinases,":[363],"circumvent":[365],"treatment":[366],"our":[372],"knowledge,":[373],"this":[374],"first":[377],"report":[378],"SFK-driven":[380],"as":[383],"an":[390],"NSCLC.":[394],"NSCLC":[402,448],"biopsies":[403],"may":[404],"guide":[405],"exploration":[407],"combination":[409],"TKIs.":[414],"Citation":[415],"Format:":[416],"Logan":[417],"C.":[418,430],"Tyler,":[419],"Nan":[420],"Chen,":[421],"Anh":[422],"T.":[423],"Le,":[424],"Hala":[425],"Nijmeh,":[426],"Liming":[427],"Bao,":[428],"Robert":[429],"Doebele.":[431],"cooperate":[435],"[abstract].":[449],"In:":[450],"Proceedings":[451],"American":[454],"Association":[455],"Cancer":[457,468],"Research":[458],"Annual":[459],"Meeting":[460],"2022;":[461],"2022":[462],"Apr":[463],"8-13.":[464],"Philadelphia":[465],"(PA):":[466],"AACR;":[467],"Res":[469],"2022;82(12_Suppl):Abstract":[470],"nr":[471],"1102.":[472]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2022-06-17T00:00:00"}