{"id":"https://openalex.org/W4391302980","doi":"https://doi.org/10.1200/jco.2024.42.4_suppl.690","title":"Mechanisms and strategies to overcome resistance to enfortumab vedotin in bladder cancer.","display_name":"Mechanisms and strategies to overcome resistance to enfortumab vedotin in bladder cancer.","publication_year":2024,"publication_date":"2024-01-29","ids":{"openalex":"https://openalex.org/W4391302980","doi":"https://doi.org/10.1200/jco.2024.42.4_suppl.690"},"language":"en","primary_location":{"id":"doi:10.1200/jco.2024.42.4_suppl.690","doi":"https://doi.org/10.1200/jco.2024.42.4_suppl.690","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.2024.42.4_suppl.690","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"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/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","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/A5031134193","display_name":"Kevin Chang","orcid":"https://orcid.org/0000-0002-6555-3592","observed_orcids":["https://orcid.org/0000-0002-6555-3592"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kevin Chang","raw_affiliation_strings":["University of California, San Francisco, San Francisco, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California, San Francisco, San Francisco, CA","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085765128","display_name":"Roshan Lodha","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1316902750","display_name":"Cleveland Clinic","ror":"https://ror.org/03xjacd83","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316902750"]},{"id":"https://openalex.org/I36373038","display_name":"Cleveland Clinic Lerner College of Medicine","ror":"https://ror.org/02x4b0932","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316902750","https://openalex.org/I36373038"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Roshan Lodha","raw_affiliation_strings":["Cleveland Clinic Lerner College of Medicine, Cleveland, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cleveland Clinic Lerner College of Medicine, Cleveland, OH","institution_ids":["https://openalex.org/I1316902750","https://openalex.org/I36373038"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5093809202","display_name":"Henry M. Delavan","orcid":"https://orcid.org/0009-0003-2571-9003","observed_orcids":["https://orcid.org/0009-0003-2571-9003"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]},{"id":"https://openalex.org/I4210167126","display_name":"UCSF Helen Diller Family Comprehensive Cancer Center","ror":"https://ror.org/05yndxy10","country_code":"US","type":"facility","lineage":["https://openalex.org/I180670191","https://openalex.org/I4210110664","https://openalex.org/I4210167126"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Henry M. Delavan","raw_affiliation_strings":["Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA","institution_ids":["https://openalex.org/I180670191","https://openalex.org/I4210167126"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5093809203","display_name":"Jenna G. Winebaum","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]},{"id":"https://openalex.org/I4210167126","display_name":"UCSF Helen Diller Family Comprehensive Cancer Center","ror":"https://ror.org/05yndxy10","country_code":"US","type":"facility","lineage":["https://openalex.org/I180670191","https://openalex.org/I4210110664","https://openalex.org/I4210167126"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jenna Winebaum","raw_affiliation_strings":["Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA","institution_ids":["https://openalex.org/I180670191","https://openalex.org/I4210167126"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046834675","display_name":"Sima P. Porten","orcid":"https://orcid.org/0000-0002-3948-4968","observed_orcids":["https://orcid.org/0000-0002-3948-4968"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sima P. Porten","raw_affiliation_strings":["University of California San Francisco, San Francisco, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California San Francisco, San Francisco, CA","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020006331","display_name":"Felix Yi-Chung Feng","orcid":"https://orcid.org/0000-0002-0963-7687","observed_orcids":["https://orcid.org/0000-0002-0963-7687","https://orcid.org/0000-0001-9756-4037"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]},{"id":"https://openalex.org/I4210167126","display_name":"UCSF Helen Diller Family Comprehensive Cancer Center","ror":"https://ror.org/05yndxy10","country_code":"US","type":"facility","lineage":["https://openalex.org/I180670191","https://openalex.org/I4210110664","https://openalex.org/I4210167126"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Felix Y Feng","raw_affiliation_strings":["Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA","institution_ids":["https://openalex.org/I180670191","https://openalex.org/I4210167126"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079611269","display_name":"Carissa Ellen Chu","orcid":"https://orcid.org/0000-0003-3065-389X","observed_orcids":["https://orcid.org/0000-0003-3065-389X"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Carissa E Chu","raw_affiliation_strings":["University of California, San Francisco, San Francisco, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California, San Francisco, San Francisco, CA","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5019176693","display_name":"Jonathan Chou","orcid":"https://orcid.org/0000-0003-1258-0391","observed_orcids":["https://orcid.org/0000-0003-1258-0391"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]},{"id":"https://openalex.org/I4210167126","display_name":"UCSF Helen Diller Family Comprehensive Cancer Center","ror":"https://ror.org/05yndxy10","country_code":"US","type":"facility","lineage":["https://openalex.org/I180670191","https://openalex.org/I4210110664","https://openalex.org/I4210167126"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jonathan Chou","raw_affiliation_strings":["Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA","institution_ids":["https://openalex.org/I180670191","https://openalex.org/I4210167126"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":10,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"42","issue":"4_suppl","first_page":"690","last_page":"690"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10458","display_name":"Bladder and Urothelial Cancer Treatments","score":0.9603999853134155,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"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/T10458","display_name":"Bladder and Urothelial Cancer Treatments","score":0.9603999853134155,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.014999999664723873,"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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.002899999963119626,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/enfortumab-vedotin","display_name":"enfortumab vedotin","score":0.9900000095367432},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.6990000009536743},{"id":"https://openalex.org/keywords/nectin-4","display_name":"nectin-4","score":0.8019999861717224},{"id":"https://openalex.org/keywords/antibody-drug-conjugates","display_name":"antibody-drug conjugates","score":0.8320000171661377},{"id":"https://openalex.org/keywords/bladder-cancer","display_name":"bladder cancer","score":0.746999979019165},{"id":"https://openalex.org/keywords/non-muscle-invasive-bladder-cancer","display_name":"non-muscle-invasive bladder cancer","score":0.8339999914169312},{"id":"https://openalex.org/keywords/metastatic-urothelial-carcinoma","display_name":"metastatic urothelial carcinoma","score":0.8870000243186951},{"id":"https://openalex.org/keywords/p-glycoprotein","display_name":"P-glycoprotein","score":0.847000002861023},{"id":"https://openalex.org/keywords/transforming-growth-factor-beta","display_name":"TGF-beta","score":0.8610000014305115},{"id":"https://openalex.org/keywords/sacituzumab-govitecan","display_name":"sacituzumab govitecan","score":0.9390000104904175},{"id":"https://openalex.org/keywords/trop2","display_name":"TROP2","score":0.6710000038146973},{"id":"https://openalex.org/keywords/chimeric-antigen-receptor-t-cells","display_name":"chimeric antigen receptor T cells","score":0.7559999823570251},{"id":"https://openalex.org/keywords/single-chain-variable-fragment","display_name":"scFv","score":0.453000009059906}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.9004333019256592},{"id":"https://openalex.org/C2780352672","wikidata":"https://www.wikidata.org/wiki/Q504775","display_name":"Bladder cancer","level":3,"score":0.5991892218589783},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.5400901436805725},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5367518663406372},{"id":"https://openalex.org/C3020745361","wikidata":"https://www.wikidata.org/wiki/Q2501186","display_name":"Urothelial cancer","level":4,"score":0.5259445309638977},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.40464943647384644},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.34519171714782715}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1200/jco.2024.42.4_suppl.690","doi":"https://doi.org/10.1200/jco.2024.42.4_suppl.690","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.2024.42.4_suppl.690","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"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/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9763000011444092}],"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/W4409689962","https://openalex.org/W4282970879","https://openalex.org/W3135248026","https://openalex.org/W4409633829","https://openalex.org/W4379336690","https://openalex.org/W4365511880","https://openalex.org/W4393075727","https://openalex.org/W7148962536","https://openalex.org/W4319334389","https://openalex.org/W4324136849"],"abstract_inverted_index":{"690":[0],"Background:":[1],"Enfortumab":[2],"vedotin":[3],"(EV)":[4],"is":[5,21,35,59],"an":[6,231,427],"antibody-drug":[7],"conjugate":[8],"(ADC)":[9],"targeting":[10],"NECTIN4,":[11,103],"a":[12,71,108,166,255,261,318,351,401],"surface":[13,381],"protein":[14],"highly":[15],"expressed":[16],"in":[17,39,142,264,292,353],"bladder":[18,46,73,94,357,387],"tumors,":[19],"and":[20,86,125,153,181,196,206,224,227,249,276,289,374,410],"currently":[22,36],"approved":[23],"for":[24,192,266],"metastatic":[25],"urothelial":[26],"carcinoma":[27],"(mUC).":[28],"Based":[29],"on":[30],"its":[31],"demonstrated":[32],"benefit,":[33],"EV":[34,65,77,121,244,296,364,385,408,431],"being":[37],"evaluated":[38],"earlier":[40],"UC":[41],"settings,":[42],"including":[43],"non-muscle":[44],"invasive":[45],"cancer":[47,74,95,358,388],"(NMIBC).":[48],"Because":[49],"ADCs":[50,417],"are":[51],"associated":[52],"with":[53,79,118,122,148,165,173,203,240],"primary":[54],"or":[55,212,220],"secondary":[56],"resistance,":[57,409],"it":[58],"crucial":[60],"to":[61,69,88,106,280,302,314,322,334,342,360,363,368,370,377,392,416],"understand":[62],"mechanisms":[63,84,413],"of":[64,76,85,102,110,116,127,135,177,185,243,257,287,306,356,379,414],"resistance.":[66,90,111,432],"We":[67],"sought":[68],"develop":[70,107,407],"preclinical":[72,352],"model":[75,109,355],"resistance":[78,369,415],"which":[80,98],"we":[81,349],"could":[82],"investigate":[83],"strategies":[87],"overcome":[89],"Methods:":[91],"The":[92,268,295,327,384],"RT112":[93,112,138,204,235,270,309,329,344],"cell":[96,225],"line,":[97],"expresses":[99],"high":[100],"levels":[101,275,278],"was":[104,365],"used":[105,132],"cells":[113,139,236,258,271,298,310,330,340,389,406],"underwent":[114],"\u201ccycles\u201d":[115,239],"treatment":[117,238,423],"5-7":[119],"days":[120],"subsequent":[123],"recovery":[124],"passaging":[126],"surviving":[128],"cells.":[129,208,282,294,345],"Each":[130],"\u201ccycle\u201d":[131],"escalating":[133,241],"doses":[134],"EV.":[136,267,307,361],"Parental":[137],"were":[140,146,163,201,215,299,311,331],"cultured":[141],"parallel.":[143],"Cell":[144],"lines":[145],"profiled":[147],"flow":[149],"cytometry,":[150],"western":[151],"blotting,":[152],"bulk":[154],"RNA":[155],"sequencing.":[156],"Second-generation":[157],"chimeric":[158],"antigen":[159],"receptor":[160],"(CAR)":[161],"T-cells":[162,214],"engineered":[164],"single":[167],"chain":[168],"fragment":[169],"variable":[170,175],"(scFv)":[171],"designed":[172],"the":[174,178,187,304,323,371,380],"regions":[176],"heavy":[179],"(VH)":[180],"light":[182],"chains":[183],"(VL)":[184],"enfortumab,":[186],"human":[188],"monoclonal":[189],"antibody":[190,320],"specific":[191],"NECTIN4.":[193,383],"Drug":[194],"dose-response":[195],"CAR":[197,213,338,394,419],"T-cell":[198],"killing":[199,335],"assays":[200],"performed":[202],"parental":[205,281,343],"EV-exposed":[207],"After":[209],"24h,":[210],"drug":[211],"added":[216],"at":[217,246,251],"indicated":[218],"concentrations":[219,242],"effector-to-target":[221],"(E:T)":[222],"ratios,":[223],"count":[226],"growth":[228],"monitored":[229],"using":[230,424],"IncuCyte":[232],"S3.":[233],"Results:":[234],"undergoing":[237],"starting":[245],"0.5":[247],"\u00b5g/ml":[248,253],"culminating":[250],"30":[252],"yielded":[254],"generation":[256],"that":[259],"exhibited":[260],"4-5-fold":[262],"increase":[263],"IC50":[265],"\u201cEV-resistant\u201d":[269],"had":[272],"comparable":[273],"NECTIN4":[274,399],"TROP2":[277],"compared":[279,341],"Preliminary":[283],"results":[284],"suggest":[285],"upregulation":[286],"P-glycoprotein":[288],"TGF-\u03b2":[290],"genes":[291],"resistant":[293,297,359,386],"less":[300],"sensitive":[301,313,391],"MMAE,":[303,373],"payload":[305,372],"EV-resistant":[308,328],"more":[312],"sacituzumab":[315],"govitecan":[316],"(SG),":[317],"Trop-2-directed":[319],"conjugated":[321],"topoisomerase":[324],"inhibitor":[325],"SN-38.":[326],"equally":[332],"susceptible":[333],"by":[336],"NECTIN4-directed":[337,393],"T":[339,395,420],"Conclusions:":[346],"In":[347],"conclusion,":[348],"developed":[350],"vitro":[354],"Resistance":[362],"largely":[366],"due":[367,376],"not":[375],"downregulation":[378],"target":[382,403],"remained":[390],"cells,":[396],"suggesting":[397],"1)":[398],"remains":[400],"relevant":[402],"even":[404],"after":[405,430],"2)":[411],"non-overlapping":[412],"versus":[418],"therapy.":[421],"Finally,":[422],"SG":[425],"represents":[426],"alternative":[428],"strategy":[429]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":4}],"updated_date":"2026-10-17T09:40:24.721904","created_date":"2024-01-30T00:00:00"}
