{"id":"https://openalex.org/W4392686331","doi":"https://doi.org/10.1158/0008-5472.c.6503351.v1","title":"Data from Combined EGFR/MET or EGFR/HSP90 Inhibition Is Effective in the Treatment of Lung Cancers Codriven by Mutant EGFR Containing T790M and MET","display_name":"Data from Combined EGFR/MET or EGFR/HSP90 Inhibition Is Effective in the Treatment of Lung Cancers Codriven by Mutant EGFR Containing T790M and MET","publication_year":2023,"publication_date":"2023-03-30","ids":{"openalex":"https://openalex.org/W4392686331","doi":"https://doi.org/10.1158/0008-5472.c.6503351.v1"},"language":"en","primary_location":{"id":"doi:10.1158/0008-5472.c.6503351.v1","doi":"https://doi.org/10.1158/0008-5472.c.6503351.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/0008-5472.c.6503351.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"http://dx.doi.org/10.1158/0008-5472.c.6503351.v1","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5100342457","display_name":"Lu Xu","orcid":"https://orcid.org/0009-0003-6743-5535","observed_orcids":["https://orcid.org/0009-0003-6743-5535","https://orcid.org/0009-0007-3921-5614","https://orcid.org/0009-0008-3827-5639"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lu Xu","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076506991","display_name":"Eiki Kikuchi","orcid":"https://orcid.org/0000-0003-4098-6321","observed_orcids":["https://orcid.org/0000-0003-4098-6321"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Eiki Kikuchi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100418663","display_name":"Chunxiao Xu","orcid":"https://orcid.org/0000-0001-5292-8052","observed_orcids":["https://orcid.org/0000-0001-5292-8052"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Chunxiao Xu","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088194700","display_name":"Hiromichi Ebi","orcid":"https://orcid.org/0000-0003-3155-7576","observed_orcids":["https://orcid.org/0000-0003-3155-7576"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Hiromichi Ebi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003183589","display_name":"Dalia Ercan","orcid":"https://orcid.org/0000-0002-2425-0691","observed_orcids":["https://orcid.org/0000-0002-2425-0691"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Dalia Ercan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044206976","display_name":"Katherine A. Cheng","orcid":"https://orcid.org/0000-0002-3375-8016","observed_orcids":["https://orcid.org/0000-0002-3375-8016"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Katherine A. Cheng","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5019306613","display_name":"Robert F. Padera","orcid":"https://orcid.org/0000-0002-4571-5494","observed_orcids":["https://orcid.org/0000-0002-4571-5494"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Robert Padera","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040093136","display_name":"Jeffrey A. Engelman","orcid":"https://orcid.org/0009-0004-0775-4523","observed_orcids":["https://orcid.org/0009-0004-0775-4523"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jeffrey A. Engelman","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5048675362","display_name":"Pasi Antero Janne","orcid":"https://orcid.org/0000-0002-7821-4928","observed_orcids":["https://orcid.org/0000-0002-7821-4928"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Pasi A. J\u00e4nne","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045419282","display_name":"Geoffrey Ira Shapiro","orcid":"https://orcid.org/0000-0002-3331-4095","observed_orcids":["https://orcid.org/0000-0002-3331-4095"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Geoffrey I. Shapiro","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012904104","display_name":"Takeshi Shimamura","orcid":"https://orcid.org/0000-0002-5402-7204","observed_orcids":["https://orcid.org/0000-0002-5402-7204"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Takeshi Shimamura","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5019034689","display_name":"Kwok\u2010Kin Wong","orcid":"https://orcid.org/0000-0001-6323-235X","observed_orcids":["https://orcid.org/0000-0001-6323-235X","https://orcid.org/0000-0003-1120-8176"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Kwok-Kin Wong","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"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":null,"issue":null,"first_page":null,"last_page":null},"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/T10755","display_name":"HER2/EGFR in Cancer Research","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"}},{"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"}}],"keywords":[{"id":"https://openalex.org/keywords/egfr","display_name":"EGFR","score":0.7390000224113464},{"id":"https://openalex.org/keywords/met","display_name":"MET","score":0.9940000176429749},{"id":"https://openalex.org/keywords/egfr-t790m-mutation","display_name":"T790M mutation","score":0.9070000052452087},{"id":"https://openalex.org/keywords/non-small-cell-lung-cancer","display_name":"non-small cell lung cancer","score":0.8100000023841858},{"id":"https://openalex.org/keywords/egfr-tyrosine-kinase-inhibitors","display_name":"EGFR tyrosine kinase inhibitors","score":0.8069999814033508},{"id":"https://openalex.org/keywords/acquired-drug-resistance","display_name":"acquired drug resistance","score":0.9340000152587891},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.7360000014305115},{"id":"https://openalex.org/keywords/met-amplification","display_name":"MET amplification","score":0.722000002861023},{"id":"https://openalex.org/keywords/hsp90-inhibition","display_name":"HSP90 inhibition","score":0.7979999780654907}],"concepts":[{"id":"https://openalex.org/C2777930144","wikidata":"https://www.wikidata.org/wiki/Q25100112","display_name":"T790M","level":5,"score":0.8686254620552063},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.6209592819213867},{"id":"https://openalex.org/C2777506169","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"EGFR inhibitors","level":4,"score":0.5517317652702332},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.5049791932106018},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.46643567085266113},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.46549901366233826},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.4148212969303131},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2796546220779419},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.2755173444747925},{"id":"https://openalex.org/C2780580887","wikidata":"https://www.wikidata.org/wiki/Q417824","display_name":"Gefitinib","level":4,"score":0.24002140760421753},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.15220418572425842},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.06284809112548828},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.06168586015701294}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/0008-5472.c.6503351.v1","doi":"https://doi.org/10.1158/0008-5472.c.6503351.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/0008-5472.c.6503351.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/0008-5472.c.6503351.v1","doi":"https://doi.org/10.1158/0008-5472.c.6503351.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/0008-5472.c.6503351.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.9940000176429749,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"score":0.7799999713897705,"display_name":"Good health and well-being","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/W2106937997","https://openalex.org/W2043552054","https://openalex.org/W2792211948","https://openalex.org/W2944067375","https://openalex.org/W3030729391","https://openalex.org/W3031530718","https://openalex.org/W2097775552","https://openalex.org/W2138536086","https://openalex.org/W1849518619","https://openalex.org/W3072989489"],"abstract_inverted_index":{"Abstract":[0],"Tyrosine":[1],"kinase":[2,26],"inhibitors":[3],"(TKI)":[4],"that":[5,62,143,197],"target":[6],"the":[7,41,53,64,77],"EGF":[8],"receptor":[9],"(EGFR)":[10],"are":[11,52],"effective":[12],"in":[13,34,110,184],"most":[14,42],"non\u2013small":[15],"cell":[16],"lung":[17,128],"carcinoma":[18],"(NSCLC)":[19],"patients":[20,206],"whose":[21],"tumors":[22,88,105,171],"harbor":[23,94],"activating":[24],"EGFR":[25,60,68,80,92,146,161,169,201],"domain":[27],"mutations.":[28],"Unfortunately,":[29],"acquired":[30,46],"resistance":[31,47,189],"eventually":[32],"emerges":[33],"these":[35,104],"chronically":[36],"treated":[37],"cancers.":[38],"Two":[39],"of":[40,45,55,66,73,79,86,187,200],"common":[43],"mechanisms":[44],"to":[48,75,84,90,120,190],"TKIs":[49,93,192],"seen":[50],"clinically":[51],"acquisition":[54],"a":[56,117],"secondary":[57],"\u201cgatekeeper\u201d":[58],"T790M":[59,96],"mutation":[61,97],"increases":[63],"affinity":[65],"mutant":[67],"for":[69,103],"ATP":[70],"and":[71,98,162,177,193,202],"activation":[72],"MET":[74,99,139,148,163,203],"offset":[76],"loss":[78],"signaling.":[81],"Although":[82],"up":[83],"one-third":[85],"patient":[87],"resistant":[89],"reversible":[91,191],"concurrent":[95,138],"amplification,":[100],"potential":[101,122],"therapies":[102,123,159],"have":[106],"not":[107,151],"been":[108],"modeled":[109],"vivo.":[111],"In":[112,156],"this":[113],"study,":[114],"we":[115],"developed":[116],"preclinical":[118,195],"platform":[119],"evaluate":[121],"by":[124,173],"generating":[125],"transgenic":[126],"mouse":[127],"cancer":[129],"models":[130],"expressing":[131],"EGFR-mutant":[132],"Del19-T790M":[133,174],"or":[134,147,175],"L858R-T790M,":[135],"each":[136],"with":[137,207],"overexpression.":[140],"We":[141],"found":[142],"monotherapy":[144],"targeting":[145,160,199],"alone":[149],"did":[150],"produce":[152],"significant":[153],"tumor":[154],"regression.":[155],"contrast,":[157],"combination":[158,198],"simultaneously":[164],"were":[165],"highly":[166],"efficacious":[167],"against":[168],"TKI\u2013resistant":[170],"codriven":[172],"L858R-T790M":[176],"MET.":[178],"Our":[179],"findings":[180],"therefore":[181],"provide":[182],"an":[183],"vivo":[185],"model":[186],"intrinsic":[188],"offer":[194],"proof-of-principle":[196],"may":[204],"benefit":[205],"NSCLC.":[208],"Cancer":[209],"Res;":[210],"72(13);":[211],"3302\u201311.":[212],"\u00a92012":[213],"AACR.":[214]},"counts_by_year":[],"updated_date":"2026-10-16T09:59:22.235173","created_date":"2025-10-10T00:00:00"}