{"id":"https://openalex.org/W4200595334","doi":"https://doi.org/10.1158/1535-7163.targ-21-p076","title":"Abstract P076: Novel mechanisms of acquired TKI resistance in ROS1+ NSCLC","display_name":"Abstract P076: Novel mechanisms of acquired TKI resistance in ROS1+ NSCLC","publication_year":2021,"publication_date":"2021-12-01","ids":{"openalex":"https://openalex.org/W4200595334","doi":"https://doi.org/10.1158/1535-7163.targ-21-p076"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.targ-21-p076","doi":"https://doi.org/10.1158/1535-7163.targ-21-p076","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1535-7163.targ-21-p076","pdf_url":null,"source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","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 Therapeutics","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/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":["2Colorado Genetics Laboratory - Anschutz Medical Campus, Aurora, CO,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Colorado Genetics Laboratory - Anschutz Medical Campus, Aurora, CO,","institution_ids":["https://openalex.org/I51713134"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085033553","display_name":"Liming Bao","orcid":"https://orcid.org/0000-0001-9400-734X","observed_orcids":["https://orcid.org/0000-0001-9400-734X"]},"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":["2Colorado Genetics Laboratory - Anschutz Medical Campus, Aurora, CO,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Colorado Genetics Laboratory - Anschutz Medical Campus, Aurora, CO,","institution_ids":["https://openalex.org/I51713134"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045688129","display_name":"Kristen M. Turner","orcid":"https://orcid.org/0000-0002-4661-3094","observed_orcids":["https://orcid.org/0000-0002-4661-3094"]},"institutions":[{"id":"https://openalex.org/I4210091888","display_name":"Boundless Bio (United States)","ror":"https://ror.org/00ck5k311","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091888"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kristen Turner","raw_affiliation_strings":["3Boundless Bio, Inc, San Diego, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Boundless Bio, Inc, San Diego, CA","institution_ids":["https://openalex.org/I4210091888"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062216939","display_name":"Jason Christianson","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210091888","display_name":"Boundless Bio (United States)","ror":"https://ror.org/00ck5k311","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091888"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jason Christianson","raw_affiliation_strings":["3Boundless Bio, Inc, San Diego, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Boundless Bio, Inc, San Diego, CA","institution_ids":["https://openalex.org/I4210091888"]}]},{"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":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"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":"20","issue":"12_Supplement","first_page":"P076","last_page":"P076"},"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/T13779","display_name":"Cancer Mechanisms and Therapy","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2734","display_name":"Pathology and Forensic Medicine"},"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/ros1-positive-non-small-cell-lung-cancer","display_name":"ROS1-positive non-small cell lung cancer","score":0.8579999804496765},{"id":"https://openalex.org/keywords/entrectinib","display_name":"entrectinib","score":0.9290000200271606},{"id":"https://openalex.org/keywords/crizotinib","display_name":"crizotinib","score":1.0},{"id":"https://openalex.org/keywords/met-amplification","display_name":"MET amplification","score":0.8169999718666077},{"id":"https://openalex.org/keywords/extrachromosomal-dna","display_name":"extrachromosomal DNA","score":0.8519999980926514},{"id":"https://openalex.org/keywords/egfr-amplification","display_name":"EGFR amplification","score":0.7160000205039978},{"id":"https://openalex.org/keywords/src-family-kinases","display_name":"Src family kinases","score":0.6200000047683716},{"id":"https://openalex.org/keywords/afatinib","display_name":"afatinib","score":0.847000002861023},{"id":"https://openalex.org/keywords/mapk-signaling","display_name":"MAPK signaling","score":0.7829999923706055},{"id":"https://openalex.org/keywords/drug-resistance-mechanisms","display_name":"drug resistance mechanisms","score":0.5199999809265137},{"id":"https://openalex.org/keywords/patient-derived-cell-lines","display_name":"patient-derived cell lines","score":0.8669999837875366}],"concepts":[{"id":"https://openalex.org/C2775999482","wikidata":"https://www.wikidata.org/wiki/Q18031208","display_name":"ROS1","level":4,"score":0.9019135236740112},{"id":"https://openalex.org/C2779422266","wikidata":"https://www.wikidata.org/wiki/Q5186964","display_name":"Crizotinib","level":4,"score":0.8564455509185791},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5950134992599487},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.49243077635765076},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.44638606905937195},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.40663760900497437},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.36479461193084717},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.3306330442428589},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.25951600074768066},{"id":"https://openalex.org/C2781182431","wikidata":"https://www.wikidata.org/wiki/Q356033","display_name":"Adenocarcinoma","level":3,"score":0.24432796239852905},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.22286826372146606},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.21578678488731384},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.12978783249855042},{"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:10.1158/1535-7163.targ-21-p076","doi":"https://doi.org/10.1158/1535-7163.targ-21-p076","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1535-7163.targ-21-p076","pdf_url":null,"source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","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 Therapeutics","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3"}],"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/W4282967840","https://openalex.org/W3083720088","https://openalex.org/W2982060134","https://openalex.org/W4295758260","https://openalex.org/W4392228472","https://openalex.org/W3165669398","https://openalex.org/W3161305664","https://openalex.org/W4379339776","https://openalex.org/W7165774746","https://openalex.org/W2332102550"],"abstract_inverted_index":{"Abstract":[0],"ROS1":[1,16,38,42,80,87,141,354,390],"tyrosine":[2],"kinase":[3,43,223],"inhibitors":[4],"(TKIs)":[5],"entrectinib":[6,104,356],"and":[7,75,96,124,134,169,189,226,238,248,254,267,327,357,370,409,463],"crizotinib":[8,108],"have":[9],"significantly":[10],"improved":[11],"outcomes":[12],"for":[13],"patients":[14,35,61,388],"with":[15,165,176,260,315,340,381,389,405],"gene":[17,194,283,303],"fusion":[18],"positive":[19],"(ROS1+)":[20],"lung":[21],"adenocarcinoma.":[22],"However,":[23],"drug":[24],"resistance":[25,56,85,352,447],"inevitably":[26],"develops,":[27],"leading":[28],"to":[29,37,73,86,99,103,116,157,200,220,250,273,291,330,353,420],"disease":[30],"progression.":[31],"Approximately":[32],"one-third":[33],"of":[34,55,60,69,78,139,214,228,236,256,263,310,351,363,376,395,444,454],"resistant":[36,145],"TKIs":[39,159,355,383],"demonstrate":[40],"on-target":[41],"domain":[44],"(KD)":[45],"mutations":[46],"(Dziadziuszko":[47],"et":[48],"al.":[49],"ESMO":[50],"2019),":[51],"but":[52,179],"the":[53,58,118,140,311,455],"mechanism":[54],"in":[57,110,143,160,233,285,297,308,324,335,387,448],"majority":[59],"remain":[62],"unknown":[63],"or":[64,107,275,299,342],"poorly":[65],"characterized.":[66],"The":[67,393],"purpose":[68],"this":[70],"study":[71],"was":[72,305],"model":[74],"characterize":[76],"mechanisms":[77,119,350,443],"acquired":[79,445],"TKI":[81,230,391,446],"resistance.":[82,392],"To":[83],"investigate":[84],"TKIs,":[88,225],"we":[89,347],"used":[90],"patient-derived":[91],"cell":[92,131,146,161,312],"lines":[93,147],"CUTO28":[94,266],"(TPM3-ROS1)":[95],"CUTO37":[97,268],"(CD74-ROS1)":[98],"generate":[100],"drug-resistant":[101],"derivatives":[102],"(CUTO28-ER,":[105],"CUTO37-ER)":[106],"(CUTO28-CR,CUTO37-CR)":[109],"vitro.":[111],"We":[112],"utilized":[113],"several":[114],"techniques":[115],"probe":[117],"driving":[120],"resistance,":[121],"including":[122],"DNA":[123,137,211],"RNA":[125],"sequencing,":[126],"fluorescence":[127],"in-situ":[128],"hybridization":[129],"(FISH),":[130],"proliferation":[132,162,237,247],"assays,":[133],"western":[135],"blotting.":[136],"sequencing":[138,412],"KD":[142],"all":[144],"did":[148],"not":[149,180,271,296,306,415],"reveal":[150],"any":[151,309],"mutations.":[152],"CUTO28-ER":[153],"cells":[154,202,217,243,269,329],"displayed":[155,218,244],"sensitivity":[156,219,245],"MET-selective":[158],"assays.":[163],"Consistent":[164],"MET":[166,187,193,364,397],"dependency,":[167],"MAPK":[168,240,322],"Akt":[170],"pathways":[171],"were":[172,270],"inhibited":[173],"by":[174],"treatment":[175],"a":[177,181,331,374],"MET-selective,":[178],"ROS1-selective,":[182],"TKI.":[183],"Western":[184],"blot":[185],"demonstrated":[186,348],"overexpression":[188],"interphase":[190],"FISH":[191,208,279],"confirmed":[192],"amplification":[195,213,284,304,362,398],"(MET:CEP7":[196,203],"ratio":[197,204,288,294],"4.2)":[198],"compared":[199,290],"parental":[201,292,337],"1.0).":[205],"Notably,":[206],"metaphase":[207],"revealed":[209,280],"extrachromosomal":[210],"(ecDNA)":[212],"MET.":[215],"CUTO28-CR":[216,286],"Src":[221],"family":[222],"(SFK)":[224],"addition":[227],"pan-HER":[229,251],"afatinib":[231],"resulted":[232],"synergistic":[234],"inhibition":[235],"downstream":[239],"signaling.":[241,378],"CUTO37-ER":[242,298],"via":[246],"signaling":[249,323],"inhibitor":[252],"afatinib,":[253],"phosphorylation":[255],"EGFR":[257,282,341],"Y845":[258],"consistent":[259,339],"Src-mediated":[261],"activation":[262],"EGFR.":[264],"Parental":[265],"sensitive":[272],"SFK":[274],"HER":[276],"inhibition.":[277],"Interphase":[278],"modest":[281],"cells\u2014(EGFR:CEP7":[287],"2.1)":[289],"(EGFR:CEP7":[293],"1.0)\u2014but":[295],"CUTO37-CR":[300,328],"cells.":[301],"HER2":[302,343],"identified":[307],"lines.":[313],"Stimulation":[314],"epidermal":[316],"growth":[317],"factor":[318],"(EGF)":[319],"markedly":[320],"enhanced":[321],"CUTO28-CR,":[325],"CUTO37-ER,":[326],"greater":[332],"extent":[333],"than":[334],"corresponding":[336],"cells,":[338],"dependence.":[344],"In":[345],"conclusion,":[346],"novel":[349],"crizotinib.":[358],"These":[359],"include":[360],"ecDNA":[361,396,402],"as":[365,373],"an":[366],"alternate":[367],"oncogene":[368],"driver":[369,375],"Src/EGFR":[371],"axis":[372],"bypass":[377],"Combination":[379],"strategies":[380],"existing":[382],"could":[384],"be":[385],"explored":[386],"discovery":[394],"is":[399,403],"particularly":[400],"intriguing;":[401],"associated":[404],"more":[406],"aggressive":[407],"cancers":[408],"next":[410],"generation":[411],"analyses":[413],"do":[414],"typically":[416],"involve":[417],"amplicon":[418],"reconstruction":[419],"detect":[421],"ecDNA.":[422],"Citation":[423],"Format:":[424],"Logan":[425],"C.":[426,440],"Tyler,":[427],"Anh":[428],"T.":[429],"Le,":[430],"Hala":[431],"Nijmeh,":[432],"Liming":[433],"Bao,":[434],"Kristen":[435],"Turner,":[436],"Jason":[437],"Christianson,":[438],"Robert":[439],"Doebele.":[441],"Novel":[442],"ROS1+":[449],"NSCLC":[450],"[abstract].":[451],"In:":[452],"Proceedings":[453],"AACR-NCI-EORTC":[456],"Virtual":[457],"International":[458],"Conference":[459],"on":[460],"Molecular":[461],"Targets":[462],"Cancer":[464,473],"Therapeutics;":[465],"2021":[466],"Oct":[467],"7-10.":[468],"Philadelphia":[469],"(PA):":[470],"AACR;":[471],"Mol":[472],"Ther":[474],"2021;20(12":[475],"Suppl):Abstract":[476],"nr":[477],"P076.":[478]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2021-12-31T00:00:00"}
