{"id":"https://openalex.org/W2385998451","doi":"https://doi.org/10.1158/1535-7163.targ-15-b52","title":"Abstract B52: Bioenergetic switch confers acquired resistance to BEZ235 in EGFR T790M-mutant non-small cell lung cancer","display_name":"Abstract B52: Bioenergetic switch confers acquired resistance to BEZ235 in EGFR T790M-mutant non-small cell lung cancer","publication_year":2015,"publication_date":"2015-12-01","ids":{"openalex":"https://openalex.org/W2385998451","doi":"https://doi.org/10.1158/1535-7163.targ-15-b52","mag":"2385998451"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.targ-15-b52","doi":"https://doi.org/10.1158/1535-7163.targ-15-b52","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1535-7163.targ-15-b52","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","is_traditional":false,"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/A5082665670","display_name":"Bhaskar Bhattacharya","orcid":"https://orcid.org/0000-0002-2833-3670","observed_orcids":["https://orcid.org/0000-0002-2833-3670"]},"institutions":[{"id":"https://openalex.org/I4405277804","display_name":"Cancer Science Institute of Singapore","ror":"https://ror.org/03yky5015","country_code":"SG","type":"facility","lineage":["https://openalex.org/I4405277804"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Bhaskar Bhattacharya","raw_affiliation_strings":["1Cancer Science Inst. of Singapore, Singapore, Singapore;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Cancer Science Inst. of Singapore, Singapore, Singapore;","institution_ids":["https://openalex.org/I4405277804"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005305257","display_name":"King Xin Koh","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405277804","display_name":"Cancer Science Institute of Singapore","ror":"https://ror.org/03yky5015","country_code":"SG","type":"facility","lineage":["https://openalex.org/I4405277804"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"King Xin Koh","raw_affiliation_strings":["1Cancer Science Inst. of Singapore, Singapore, Singapore;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Cancer Science Inst. of Singapore, Singapore, Singapore;","institution_ids":["https://openalex.org/I4405277804"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077251608","display_name":"Mohamed Feroz Mohamed Omar","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405277804","display_name":"Cancer Science Institute of Singapore","ror":"https://ror.org/03yky5015","country_code":"SG","type":"facility","lineage":["https://openalex.org/I4405277804"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Mohamed Feroz Mohamed Omar","raw_affiliation_strings":["1Cancer Science Inst. of Singapore, Singapore, Singapore;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Cancer Science Inst. of Singapore, Singapore, Singapore;","institution_ids":["https://openalex.org/I4405277804"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Sarah Low","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405277804","display_name":"Cancer Science Institute of Singapore","ror":"https://ror.org/03yky5015","country_code":"SG","type":"facility","lineage":["https://openalex.org/I4405277804"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Sarah Low","raw_affiliation_strings":["1Cancer Science Inst. of Singapore, Singapore, Singapore;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Cancer Science Inst. of Singapore, Singapore, Singapore;","institution_ids":["https://openalex.org/I4405277804"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040362387","display_name":"Juleen Tan","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405277804","display_name":"Cancer Science Institute of Singapore","ror":"https://ror.org/03yky5015","country_code":"SG","type":"facility","lineage":["https://openalex.org/I4405277804"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Juleen Tan","raw_affiliation_strings":["1Cancer Science Inst. of Singapore, Singapore, Singapore;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Cancer Science Inst. of Singapore, Singapore, Singapore;","institution_ids":["https://openalex.org/I4405277804"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008190977","display_name":"Nur Sabrina Sapari","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405277804","display_name":"Cancer Science Institute of Singapore","ror":"https://ror.org/03yky5015","country_code":"SG","type":"facility","lineage":["https://openalex.org/I4405277804"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Nur Sabrina Sapari","raw_affiliation_strings":["1Cancer Science Inst. of Singapore, Singapore, Singapore;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Cancer Science Inst. of Singapore, Singapore, Singapore;","institution_ids":["https://openalex.org/I4405277804"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111624624","display_name":"Barry J. Iacopetta","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I177877127","display_name":"The University of Western Australia","ror":"https://ror.org/047272k79","country_code":"AU","type":"education","lineage":["https://openalex.org/I177877127"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Barry Iacopetta","raw_affiliation_strings":["2University of Western Australia, Perth, Australia;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2University of Western Australia, Perth, Australia;","institution_ids":["https://openalex.org/I177877127"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032293215","display_name":"Ross Andrew Soo","orcid":"https://orcid.org/0000-0002-3053-3997","observed_orcids":["https://orcid.org/0000-0002-3053-3997"]},"institutions":[{"id":"https://openalex.org/I4405277804","display_name":"Cancer Science Institute of Singapore","ror":"https://ror.org/03yky5015","country_code":"SG","type":"facility","lineage":["https://openalex.org/I4405277804"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Ross Soo","raw_affiliation_strings":["1Cancer Science Inst. of Singapore, Singapore, Singapore;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Cancer Science Inst. of Singapore, Singapore, Singapore;","institution_ids":["https://openalex.org/I4405277804"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014075696","display_name":"Mounia Beloueche\u2010Babari","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Mounia Beloueche-Babari","raw_affiliation_strings":["3The Institute of Cancer Research, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3The Institute of Cancer Research, London, United Kingdom","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5052071706","display_name":"Richie Soong","orcid":"https://orcid.org/0000-0002-0152-1225","observed_orcids":["https://orcid.org/0000-0002-0152-1225"]},"institutions":[{"id":"https://openalex.org/I4405277804","display_name":"Cancer Science Institute of Singapore","ror":"https://ror.org/03yky5015","country_code":"SG","type":"facility","lineage":["https://openalex.org/I4405277804"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Richie Soong","raw_affiliation_strings":["1Cancer Science Inst. of Singapore, Singapore, Singapore;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Cancer Science Inst. of Singapore, Singapore, Singapore;","institution_ids":["https://openalex.org/I4405277804"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":3,"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":"14","issue":"12_Supplement_2","first_page":"B52","last_page":"B52"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.9901999831199646,"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":0.9901999831199646,"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.0066999997943639755,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"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/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.0012000000569969416,"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/acquired-drug-resistance","display_name":"acquired drug resistance","score":0.9160000085830688},{"id":"https://openalex.org/keywords/bez235","display_name":"BEZ235","score":0.984000027179718},{"id":"https://openalex.org/keywords/pi3k-mtor-inhibitors","display_name":"PI3K/mTOR inhibitors","score":0.8669999837875366},{"id":"https://openalex.org/keywords/egfr-t790m-mutation","display_name":"T790M mutation","score":0.902999997138977},{"id":"https://openalex.org/keywords/non-small-cell-lung-cancer","display_name":"non-small cell lung cancer","score":0.984000027179718},{"id":"https://openalex.org/keywords/h1975-cells","display_name":"H1975 cells","score":0.8349999785423279},{"id":"https://openalex.org/keywords/mitochondrial-dna-depletion","display_name":"mitochondrial DNA depletion","score":0.6769999861717224},{"id":"https://openalex.org/keywords/glycolysis","display_name":"glycolysis","score":0.7649999856948853},{"id":"https://openalex.org/keywords/monocarboxylate-transporters","display_name":"monocarboxylate transporters","score":0.9049999713897705},{"id":"https://openalex.org/keywords/3-bromopyruvate","display_name":"3-bromopyruvate","score":0.7789999842643738},{"id":"https://openalex.org/keywords/oxygen-consumption-rate","display_name":"oxygen consumption rate","score":0.7089999914169312},{"id":"https://openalex.org/keywords/reactive-oxygen-species","display_name":"reactive oxygen species","score":0.6309999823570251},{"id":"https://openalex.org/keywords/pten","display_name":"PTEN","score":0.33399999141693115}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.685202419757843},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.5509046912193298},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.4886055588722229},{"id":"https://openalex.org/C2777609662","wikidata":"https://www.wikidata.org/wiki/Q416356","display_name":"PTEN","level":4,"score":0.4425313472747803},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.43325376510620117},{"id":"https://openalex.org/C81089528","wikidata":"https://www.wikidata.org/wiki/Q5134986","display_name":"clone (Java method)","level":3,"score":0.41484999656677246},{"id":"https://openalex.org/C2776907736","wikidata":"https://www.wikidata.org/wiki/Q408634","display_name":"Ethidium bromide","level":3,"score":0.4114648699760437},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.37489262223243713},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.36506909132003784},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.24916023015975952},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.19167912006378174},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.12711769342422485}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1535-7163.targ-15-b52","doi":"https://doi.org/10.1158/1535-7163.targ-15-b52","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1535-7163.targ-15-b52","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":[{"score":0.98580002784729,"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/W1965087096","https://openalex.org/W2769306677","https://openalex.org/W7139794775","https://openalex.org/W2955660446","https://openalex.org/W3014018540","https://openalex.org/W3180538815","https://openalex.org/W2399922602","https://openalex.org/W2033577857","https://openalex.org/W2079846804","https://openalex.org/W2492851122"],"abstract_inverted_index":{"Abstract":[0],"Introduction:":[1],"Acquired":[2,52],"resistance":[3,252,318,336,376],"(AQR)":[4],"continues":[5],"to":[6,24,41,44,65,153,165,179,231,239,317,319,344,377],"be":[7],"source":[8],"of":[9,55,62,69,126,211,220,253,310,389],"treatment":[10,245],"failure":[11],"in":[12,31,48,217,257,313,379],"EGFR":[13,32,42,380],"inhibitor":[14,27],"therapy":[15],"and":[16,76,102,168,194,248,270,275,290,321,396],"subsequent":[17],"second-line":[18],"strategies.":[19],"In":[20],"this":[21,49],"study,":[22],"AQR":[23,47,224,234,254,298],"the":[25,113,182,218,223,240,251,260,282,390],"PI3K/mTOR":[26],"BEZ235":[28,249,378],"was":[29,97,119,130,215,262],"generated":[30,58,141],"T790M":[33],"non-small":[34,382],"cell":[35,383],"lung":[36,384],"cancer":[37],"(NSCLC)":[38],"cells":[39,64,156,235,259,315,332],"refractory":[40],"inhibitors":[43,170],"better":[45],"understand":[46],"setting.":[50],"Methods:":[51],"resistant":[53,138,164],"clones":[54,139,162,183,225,265,283,299],"H1975":[56,63,155],"were":[57,79,88,110,140,163,236],"by":[59,72,132],"continual":[60],"exposure":[61],"parental":[66,154,180,228,232,258,314],"IC50":[67,145],"concentrations":[68],"BEZ235,":[70],"followed":[71],"monoclonal":[73],"selection.":[74],"Phenotypic":[75],"protein":[77],"analysis":[78,96,118,199,279],"carried":[80,98,120],"out":[81,99,121],"using":[82,90,100,112],"standard":[83],"techniques.":[84],"Differentially":[85],"expressed":[86,206],"genes":[87],"determined":[89],"Affymetrix":[91],"Gene":[92,197],"1.0ST":[93],"analysis.":[94],"Combination":[95,244],"Chou":[101],"Talalay's":[103],"median-effect":[104],"equation.":[105],"Oxygen":[106],"consumption":[107],"rates":[108],"(OCR)":[109],"measured":[111],"Seahorse":[114],"XFp":[115],"analyzer.":[116],"Metabolomic":[117,278],"with":[122,142,246,294],"1H":[123],"NMR.":[124],"Depletion":[125,309],"mitochondrial":[127,306,311,342],"DNA":[128,312],"(mtDNA)":[129],"achieved":[131],"ethidium":[133],"bromide":[134],"treatment.":[135],"Results:":[136],"Two":[137],"stably":[143],"higher":[144,267],"values":[146],"(Clone":[147],"5.2":[148],"\u03bcM,":[149],"Clone":[150],"6":[151,159],"7.8\u03bcM)":[152],"(0.32\u03bcM)":[157],"after":[158],"months.":[160],"The":[161,297],"other":[166],"PI3K":[167,320],"mTOR":[169,322],"but":[171,226,324],"not":[172,227,325],"chemotherapeutic":[173],"drugs,":[174],"indicating":[175],"class-specific":[176],"resistance.":[177],"Compared":[178,230],"cells,":[181,233,255],"exhibited":[184],"a":[185,338],"reduced":[186,192],"G1":[187],"block,":[188],"increased":[189,195,285],"migratory":[190],"capability,":[191],"PTEN":[193],"p-AKT.":[196],"array":[198],"revealed":[200],"monocarboxylate":[201],"transporters":[202],"as":[203],"top":[204],"differentially":[205],"genes,":[207],"prompting":[208],"an":[209],"investigation":[210],"glycolytic":[212,241],"status.":[213],"Proliferation":[214],"inhibited":[216],"absence":[219],"glucose":[221],"for":[222],"cells.":[229],"more":[237],"sensitive":[238],"inhibitor,":[242],"3BP.":[243],"3BP":[247],"reversed":[250],"while":[256],"combination":[261],"antagonistic.":[263],"Resistant":[264],"had":[266,284,301],"extracellular":[268],"lactate,":[269,288],"lower":[271,302],"reactive":[272],"oxygen":[273],"species":[274],"ATP":[276],"levels.":[277],"indicated":[280],"that":[281,331],"intracellular":[286],"glucose,":[287],"NADH":[289],"glutamine":[291],"levels,":[292],"consistent":[293],"enhanced":[295],"glycolysis.":[296,345],"also":[300],"OCR,":[303],"reflecting":[304],"impaired":[305],"respiratory":[307],"function.":[308],"led":[316],"inhibitors,":[323],"cisplatin.":[326],"Conclusion:":[327],"These":[328],"results":[329],"highlight":[330],"could":[333],"acquire":[334],"drug":[335],"through":[337],"bioenergetics":[339],"switch":[340,373],"from":[341],"respiration":[343],"Citation":[346],"Format:":[347],"Bhaskar":[348],"Bhattacharya,":[349],"King":[350],"Xin":[351],"Koh,":[352],"Mohamed":[353,355],"Feroz":[354],"Omar,":[356],"Sarah":[357],"Low,":[358],"Juleen":[359],"Tan,":[360],"Nur":[361],"Sabrina":[362],"Sapari,":[363],"Barry":[364],"Iacopetta,":[365],"Ross":[366],"Soo,":[367],"Mounia":[368],"Beloueche-Babari,":[369],"Richie":[370],"Soong.":[371],"Bioenergetic":[372],"confers":[374],"acquired":[375],"T790M-mutant":[381],"cancer.":[385],"[abstract].":[386],"In:":[387],"Proceedings":[388],"AACR-NCI-EORTC":[391],"International":[392],"Conference:":[393],"Molecular":[394],"Targets":[395],"Cancer":[397,408],"Therapeutics;":[398],"2015":[399],"Nov":[400],"5-9;":[401],"Boston,":[402],"MA.":[403],"Philadelphia":[404],"(PA):":[405],"AACR;":[406],"Mol":[407],"Ther":[409],"2015;14(12":[410],"Suppl":[411],"2):Abstract":[412],"nr":[413],"B52.":[414]},"counts_by_year":[],"updated_date":"2026-09-29T14:09:16.559479","created_date":"2016-06-24T00:00:00"}