{"id":"https://openalex.org/W4392689755","doi":"https://doi.org/10.1158/2159-8290.c.6546653","title":"Data from AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer","display_name":"Data from AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer","publication_year":2023,"publication_date":"2023-04-03","ids":{"openalex":"https://openalex.org/W4392689755","doi":"https://doi.org/10.1158/2159-8290.c.6546653"},"language":"en","primary_location":{"id":"doi:10.1158/2159-8290.c.6546653","doi":"https://doi.org/10.1158/2159-8290.c.6546653","is_oa":true,"landing_page_url":"https://doi.org/10.1158/2159-8290.c.6546653","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":"https://doi.org/10.1158/2159-8290.c.6546653","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5026352956","display_name":"Darren A.E. Cross","orcid":"https://orcid.org/0000-0002-5227-2871","observed_orcids":["https://orcid.org/0000-0002-5227-2871"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Darren A.E. Cross","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109386587","display_name":"Susan E. Ashton","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Susan E. Ashton","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046261528","display_name":"Serban Ghiorghiu","orcid":"https://orcid.org/0009-0006-6879-9113","observed_orcids":["https://orcid.org/0009-0006-6879-9113"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Serban Ghiorghiu","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032576859","display_name":"Cath Eberlein","orcid":"https://orcid.org/0000-0002-7357-7789","observed_orcids":["https://orcid.org/0000-0002-7357-7789"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Cath Eberlein","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037844360","display_name":"Caroline A. Nebhan","orcid":"https://orcid.org/0000-0002-9402-7284","observed_orcids":["https://orcid.org/0000-0002-9402-7284"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Caroline A. Nebhan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5048353122","display_name":"Paula J. Spitzler","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Paula J. Spitzler","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072499136","display_name":"Jonathon P. Orme","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jonathon P. Orme","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5019998609","display_name":"M. Raymond V. Finlay","orcid":"https://orcid.org/0000-0003-1402-193X","observed_orcids":["https://orcid.org/0000-0003-1402-193X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"M. Raymond V. Finlay","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5084047203","display_name":"Richard A. Ward","orcid":"https://orcid.org/0000-0002-2310-9477","observed_orcids":["https://orcid.org/0000-0002-2310-9477"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Richard A. Ward","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112905629","display_name":"Martine J. Mellor","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Martine J. Mellor","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Gareth Hughes","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gareth Hughes","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025708687","display_name":"Amar Rahi","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Amar Rahi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111628033","display_name":"Vivien N. Jacobs","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Vivien N. Jacobs","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086276533","display_name":"Monica Red Brewer","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Monica Red Brewer","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050389295","display_name":"Eiki Ichihara","orcid":"https://orcid.org/0000-0002-2966-106X","observed_orcids":["https://orcid.org/0000-0002-2966-106X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Eiki Ichihara","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100429015","display_name":"Jing Mei Sun","orcid":"https://orcid.org/0000-0003-1905-5127","observed_orcids":["https://orcid.org/0000-0003-1905-5127"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jing Sun","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061753589","display_name":"Hailing Jin","orcid":"https://orcid.org/0000-0001-5778-5193","observed_orcids":["https://orcid.org/0000-0001-5778-5193"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Hailing Jin","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5089604553","display_name":"Peter G. Ballard","orcid":"https://orcid.org/0000-0003-2024-5219","observed_orcids":["https://orcid.org/0000-0003-2024-5219"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Peter Ballard","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069468694","display_name":"Katherine J. Al-Kadhimi","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Katherine Al-Kadhimi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032382796","display_name":"Rachel A. Rowlinson","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rachel Rowlinson","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059691963","display_name":"Teresa C. M. Klinowska","orcid":"https://orcid.org/0000-0003-1997-7340","observed_orcids":["https://orcid.org/0000-0003-1997-7340"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Teresa Klinowska","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070457926","display_name":"Graham H.P. Richmond","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Graham H.P. Richmond","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070927117","display_name":"Mireille Cantarini","orcid":"https://orcid.org/0000-0002-9593-9541","observed_orcids":["https://orcid.org/0000-0002-9593-9541"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mireille Cantarini","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100638261","display_name":"Dong\u2010Wan Kim","orcid":"https://orcid.org/0000-0001-5124-7132","observed_orcids":["https://orcid.org/0000-0001-5124-7132"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Dong-Wan Kim","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055792960","display_name":"Malcolm Ranson","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Malcolm R. Ranson","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5062616992","display_name":"William J. Pao","orcid":"https://orcid.org/0000-0002-9888-0733","observed_orcids":["https://orcid.org/0000-0002-9888-0733"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"William Pao","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/osimertinib","display_name":"osimertinib","score":0.9990000128746033},{"id":"https://openalex.org/keywords/egfr-tyrosine-kinase-inhibitors","display_name":"EGFR tyrosine kinase inhibitors","score":0.8579999804496765},{"id":"https://openalex.org/keywords/egfr-t790m-mutation","display_name":"T790M mutation","score":0.9350000023841858},{"id":"https://openalex.org/keywords/egfr-mutant-non-small-cell-lung-cancer","display_name":"EGFR-mutant non-small cell lung cancer","score":0.9010000228881836},{"id":"https://openalex.org/keywords/acquired-drug-resistance","display_name":"acquired drug resistance","score":0.7689999938011169},{"id":"https://openalex.org/keywords/irreversible-kinase-inhibitors","display_name":"irreversible kinase inhibitors","score":0.7070000171661377},{"id":"https://openalex.org/keywords/third-generation-egfr-tki","display_name":"third-generation EGFR-TKI","score":0.7870000004768372}],"concepts":[{"id":"https://openalex.org/C2777930144","wikidata":"https://www.wikidata.org/wiki/Q25100112","display_name":"T790M","level":5,"score":0.8762787580490112},{"id":"https://openalex.org/C2777506169","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"EGFR inhibitors","level":4,"score":0.6059470772743225},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.5973429679870605},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.51670241355896},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5026917457580566},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4293564558029175},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3507418632507324},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.34383559226989746},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.334697961807251},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.20820754766464233},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.20747613906860352},{"id":"https://openalex.org/C2780580887","wikidata":"https://www.wikidata.org/wiki/Q417824","display_name":"Gefitinib","level":4,"score":0.18288880586624146}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1158/2159-8290.c.6546653","doi":"https://doi.org/10.1158/2159-8290.c.6546653","is_oa":true,"landing_page_url":"https://doi.org/10.1158/2159-8290.c.6546653","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"},{"id":"doi:10.1158/2159-8290.c.6546653.v1","doi":"https://doi.org/10.1158/2159-8290.c.6546653.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/2159-8290.c.6546653.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:10.1158/2159-8290.c.6546653","doi":"https://doi.org/10.1158/2159-8290.c.6546653","is_oa":true,"landing_page_url":"https://doi.org/10.1158/2159-8290.c.6546653","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":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9789000153541565}],"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/W2088540000","https://openalex.org/W7098745884","https://openalex.org/W2066659324","https://openalex.org/W2155427322","https://openalex.org/W2265752705","https://openalex.org/W1977819594","https://openalex.org/W1937437568","https://openalex.org/W7221169272","https://openalex.org/W2260046511","https://openalex.org/W1904060183"],"abstract_inverted_index":{"Abstract":[0],"First-generation":[1],"EGFR":[2,36,72,83,110,153,167],"tyrosine":[3],"kinase":[4],"inhibitors":[5],"(EGFR":[6],"TKI)":[7],"provide":[8],"significant":[9],"clinical":[10,193],"benefit":[11],"in":[12,95,103,119,180,208],"patients":[13,130],"with":[14,105,131,190],"advanced":[15,132],"EGFR-mutant":[16,120],"(EGFRm+)":[17],"non\u2013small":[18],"cell":[19,101],"lung":[20],"cancer":[21],"(NSCLC).":[22],"Patients":[23],"ultimately":[24],"develop":[25],"disease":[26],"progression,":[27],"often":[28],"driven":[29],"by":[30],"acquisition":[31],"of":[32,51,128,140,147],"a":[33,42,76,148,181],"second":[34],"T790M":[35,56],"TKI":[37],"resistance":[38,57],"mutation.":[39],"AZD9291":[40,175],"is":[41,66,136,176,206],"novel":[43,149],"oral,":[44],"potent,":[45],"and":[46,55,74,92,98,115,123,158,163],"selective":[47],"third-generation":[48,71,152],"irreversible":[49],"inhibitor":[50],"both":[52,96,161],"EGFRm+":[53,97,133],"sensitizing":[54,162],"mutants":[58],"that":[59,156],"spares":[60],"wild-type":[61,109,173],"EGFR.":[62,174],"This":[63,204,211],"mono-anilino\u2013pyrimidine":[64],"compound":[65],"structurally":[67,150],"distinct":[68,151],"from":[69,80],"other":[70],"TKIs":[73],"offers":[75],"pharmacologically":[77],"differentiated":[78],"profile":[79],"earlier":[81],"generation":[82],"TKIs.":[84],"Preclinically,":[85],"the":[86,145,187,209],"drug":[87],"potently":[88],"inhibits":[89],"signaling":[90],"pathways":[91],"cellular":[93],"growth":[94],"EGFRm+/T790M+":[99],"mutant":[100,166],"lines":[102],"vitro,":[104],"lower":[106],"activity":[107,171],"against":[108],"lines,":[111],"translating":[112],"into":[113],"profound":[114],"sustained":[116],"tumor":[117,121],"regression":[118],"xenograft":[122],"transgenic":[124],"models.":[125],"The":[126],"treatment":[127],"2":[129],"T790M+":[134,165],"NSCLC":[135],"described":[137],"as":[138],"proof":[139],"principle.":[141],"Significance:":[142],"We":[143],"report":[144],"development":[146],"TKI,":[154],"AZD9291,":[155],"irreversibly":[157],"selectively":[159],"targets":[160],"resistant":[164],"while":[168],"harboring":[169],"less":[170],"toward":[172],"showing":[177],"promising":[178],"responses":[179],"phase":[182],"I":[183],"trial":[184],"even":[185],"at":[186],"first-dose":[188],"level,":[189],"first":[191],"published":[192],"proof-of-principle":[194],"validation":[195],"being":[196],"presented.":[197],"Cancer":[198],"Discov;":[199],"4(9);":[200],"1046\u201361.":[201],"\u00a92014":[202],"AACR.":[203],"article":[205],"highlighted":[207],"In":[210],"Issue":[212],"feature,":[213],"p.":[214],"973":[215]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2024-03-13T00:00:00"}
