{"id":"https://openalex.org/W2063629211","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-210","title":"Abstract LB-210: Impact of ABC-transporters in the blood-brain barrier on the efficacy of the PARP inhibitor ABT-888 against transplanted and spontaneous murine brain tumors","display_name":"Abstract LB-210: Impact of ABC-transporters in the blood-brain barrier on the efficacy of the PARP inhibitor ABT-888 against transplanted and spontaneous murine brain tumors","publication_year":2011,"publication_date":"2011-04-01","ids":{"openalex":"https://openalex.org/W2063629211","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-210","mag":"2063629211"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2011-lb-210","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-210","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2011-lb-210","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"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/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":"Cancer Research","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":null,"display_name":"Lin Fan","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I2898336195","display_name":"The Netherlands Cancer Institute","ror":"https://ror.org/03xqtf034","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2898336195"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Lin Fan","raw_affiliation_strings":["1Netherlands Cancer Institute, Amsterdam, Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Netherlands Cancer Institute, Amsterdam, Netherlands","institution_ids":["https://openalex.org/I2898336195"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039593027","display_name":"Mark C. de Gooijer","orcid":"https://orcid.org/0000-0002-2812-991X","observed_orcids":["https://orcid.org/0000-0002-2812-991X"]},"institutions":[{"id":"https://openalex.org/I2898336195","display_name":"The Netherlands Cancer Institute","ror":"https://ror.org/03xqtf034","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2898336195"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Mark C. de Gooijer","raw_affiliation_strings":["1Netherlands Cancer Institute, Amsterdam, Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Netherlands Cancer Institute, Amsterdam, Netherlands","institution_ids":["https://openalex.org/I2898336195"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5027371881","display_name":"Jan Hendrik Beumer","orcid":"https://orcid.org/0000-0002-8978-9401","observed_orcids":["https://orcid.org/0000-0002-8978-9401"]},"institutions":[{"id":"https://openalex.org/I4210128526","display_name":"UPMC Hillman Cancer Center","ror":"https://ror.org/03bw34a45","country_code":"US","type":"facility","lineage":["https://openalex.org/I170201317","https://openalex.org/I4210128526"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jan H. Beumer","raw_affiliation_strings":["2Pittsburgh Cancer Institute The Hillman Cancer Center, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Pittsburgh Cancer Institute The Hillman Cancer Center, Pittsburgh, PA","institution_ids":["https://openalex.org/I4210128526"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034949122","display_name":"Susan M. Christner","orcid":"https://orcid.org/0009-0005-9139-888X","observed_orcids":["https://orcid.org/0009-0005-9139-888X"]},"institutions":[{"id":"https://openalex.org/I4210128526","display_name":"UPMC Hillman Cancer Center","ror":"https://ror.org/03bw34a45","country_code":"US","type":"facility","lineage":["https://openalex.org/I170201317","https://openalex.org/I4210128526"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Susan M. Christner","raw_affiliation_strings":["2Pittsburgh Cancer Institute The Hillman Cancer Center, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Pittsburgh Cancer Institute The Hillman Cancer Center, Pittsburgh, PA","institution_ids":["https://openalex.org/I4210128526"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062227574","display_name":"Jos H. Beijnen","orcid":"https://orcid.org/0000-0003-0118-561X","observed_orcids":["https://orcid.org/0000-0003-0118-561X"]},"institutions":[{"id":"https://openalex.org/I2898336195","display_name":"The Netherlands Cancer Institute","ror":"https://ror.org/03xqtf034","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2898336195"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Jos H. Beijnen","raw_affiliation_strings":["1Netherlands Cancer Institute, Amsterdam, Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Netherlands Cancer Institute, Amsterdam, Netherlands","institution_ids":["https://openalex.org/I2898336195"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5034151807","display_name":"Olaf van Tellingen","orcid":"https://orcid.org/0000-0002-1037-6269","observed_orcids":["https://orcid.org/0000-0002-1037-6269"]},"institutions":[{"id":"https://openalex.org/I2898336195","display_name":"The Netherlands Cancer Institute","ror":"https://ror.org/03xqtf034","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2898336195"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Olaf Van Tellingen","raw_affiliation_strings":["1Netherlands Cancer Institute, Amsterdam, Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Netherlands Cancer Institute, Amsterdam, Netherlands","institution_ids":["https://openalex.org/I2898336195"]}]}],"institutions":[],"countries_distinct_count":2,"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":"71","issue":"8_Supplement","first_page":"LB","last_page":"210"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.9585000276565552,"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"}},"topics":[{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.9585000276565552,"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/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.025200000032782555,"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/T11872","display_name":"Barrier Structure and Function Studies","score":0.004999999888241291,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/veliparib","display_name":"veliparib","score":0.9850000143051147},{"id":"https://openalex.org/keywords/parp-inhibitors","display_name":"PARP inhibitors","score":0.9010000228881836},{"id":"https://openalex.org/keywords/abc-transporters","display_name":"ABC transporters","score":0.8809999823570251},{"id":"https://openalex.org/keywords/blood-brain-barrier","display_name":"blood-brain barrier","score":0.9259999990463257},{"id":"https://openalex.org/keywords/p-glycoprotein","display_name":"P-glycoprotein","score":0.9419999718666077},{"id":"https://openalex.org/keywords/abcg2","display_name":"ABCG2","score":0.9990000128746033},{"id":"https://openalex.org/keywords/temozolomide","display_name":"temozolomide","score":0.9150000214576721},{"id":"https://openalex.org/keywords/glioma","display_name":"glioma","score":0.8339999914169312},{"id":"https://openalex.org/keywords/brain-penetration","display_name":"brain penetration","score":0.6110000014305115},{"id":"https://openalex.org/keywords/elacridar","display_name":"elacridar","score":0.8529999852180481},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.6980000138282776},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.5559999942779541},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.5659999847412109},{"id":"https://openalex.org/keywords/brain-tumors","display_name":"brain tumors","score":0.3630000054836273},{"id":"https://openalex.org/keywords/dna-repair","display_name":"DNA repair","score":0.4779999852180481}],"concepts":[{"id":"https://openalex.org/C2781312401","wikidata":"https://www.wikidata.org/wiki/Q7919041","display_name":"Veliparib","level":5,"score":0.8587151169776917},{"id":"https://openalex.org/C2777389519","wikidata":"https://www.wikidata.org/wiki/Q425088","display_name":"Temozolomide","level":3,"score":0.8101583123207092},{"id":"https://openalex.org/C2778227246","wikidata":"https://www.wikidata.org/wiki/Q1365309","display_name":"Glioma","level":2,"score":0.6848272681236267},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6100717186927795},{"id":"https://openalex.org/C2779138821","wikidata":"https://www.wikidata.org/wiki/Q7118227","display_name":"PARP inhibitor","level":5,"score":0.5974768996238708},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5917177200317383},{"id":"https://openalex.org/C2779130545","wikidata":"https://www.wikidata.org/wiki/Q233309","display_name":"Brain tumor","level":2,"score":0.49141037464141846},{"id":"https://openalex.org/C2778402981","wikidata":"https://www.wikidata.org/wiki/Q221694","display_name":"Blood\u2013brain barrier","level":3,"score":0.4212692975997925},{"id":"https://openalex.org/C512196","wikidata":"https://www.wikidata.org/wiki/Q4650095","display_name":"Abcg2","level":5,"score":0.4116581678390503},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3733377456665039},{"id":"https://openalex.org/C44312359","wikidata":"https://www.wikidata.org/wiki/Q286958","display_name":"ATP-binding cassette transporter","level":4,"score":0.3477925658226013},{"id":"https://openalex.org/C149011108","wikidata":"https://www.wikidata.org/wiki/Q652985","display_name":"Transporter","level":3,"score":0.3351263999938965},{"id":"https://openalex.org/C182979987","wikidata":"https://www.wikidata.org/wiki/Q3907241","display_name":"Poly ADP ribose polymerase","level":4,"score":0.3015504479408264},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.28520667552948},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.21287402510643005},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.13409340381622314},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.0765346884727478},{"id":"https://openalex.org/C529278444","wikidata":"https://www.wikidata.org/wiki/Q47273","display_name":"Central nervous system","level":2,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0},{"id":"https://openalex.org/C82381507","wikidata":"https://www.wikidata.org/wiki/Q416878","display_name":"Polymerase","level":3,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2011-lb-210","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-210","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2011-lb-210","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"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/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":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":1.0}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W1997502178","https://openalex.org/W2108062634","https://openalex.org/W1972136715","https://openalex.org/W2595193895","https://openalex.org/W3162115215","https://openalex.org/W2131670056","https://openalex.org/W2288511411","https://openalex.org/W2891226413","https://openalex.org/W2892990137","https://openalex.org/W2805729137"],"abstract_inverted_index":{"Abstract":[0],"Introduction:":[1],"ABT-888":[2,40,162,185,233,246,303,328,370,403,425],"(veliparib)":[3],"is":[4,10,49,75,94,404],"a":[5,66,214,226,321],"potent":[6],"PARP":[7,17],"inhibitor":[8],"and":[9,33,78,102,116,143,156,204,234,253,284,290,309,369,412],"currently":[11],"in":[12,35,59,84,123,152,167,194,247,279,307,340,365,426],"phase":[13],"2":[14],"clinical":[15],"trials.":[16],"inhibitors":[18],"enhance":[19,384],"the":[20,28,73,90,105,119,124,127,182,277,325,332,399,408,422,439,444],"activity":[21],"of":[22,31,39,72,108,121,129,146,179,184,245,255,270,302,313,334,348,396,402,410,424,438,443],"DNA":[23,36],"damaging":[24],"therapies,":[25],"due":[26],"to":[27,296,383],"critical":[29],"function":[30],"PARP-1":[32],"PARP-2":[34],"repair.":[37],"Combination":[38],"with":[41,169,196,213,236,363,367],"radiation-temozolomide":[42],"(TMZ)":[43],"chemotherapy":[44],"for":[45,190,287,447],"glioma":[46,63,136,216,229,337],"patient":[47],"treatment":[48],"receiving":[50],"considerable":[51],"interest":[52],"because":[53],"this":[54,318],"combination":[55,131,168,195,366],"has":[56,149],"shown":[57,99],"promise":[58],"preclinical":[60],"models.":[61,137],"High-grade":[62],"patients":[64],"have":[65,98,111],"very":[67],"poor":[68],"prognosis.":[69],"Complete":[70],"resection":[71],"tumor":[74,81],"always":[76],"impossible":[77],"many":[79],"remaining":[80],"cells":[82,338],"reside":[83],"surrounding":[85],"normal":[86],"brain":[87,106,400],"tissue":[88],"where":[89],"blood-brain":[91],"barrier":[92],"(BBB)":[93],"still":[95],"functional.":[96],"We":[97,110],"that":[100,209,417],"ABCB1":[101],"ABCG2":[103],"limit":[104],"penetration":[107,401],"ABT-888.":[109],"extended":[112],"our":[113],"pharmacokinetic":[114],"studies":[115,222,415],"are":[117],"investigating":[118],"impact":[120,178],"ABC-transporters":[122,180,387,419],"BBB":[125],"on":[126,181,324],"efficacy":[128,183,221,333],"ABT-888/TMZ":[130],"therapy":[132],"using":[133,202,225],"sophisticated":[134],"murine":[135,215],"Methods:":[138],"Drug":[139,171],"disposition":[140],"after":[141,267],"i.v.":[142,268],"p.o.":[144],"administration":[145,269],"10":[147,271,358],"mg/kg":[148,241,272],"been":[150],"determined":[151,174],"wildtype":[153],"(WT),":[154],"single":[155,258,260],"compound":[157,263],"ABC-transporter":[158],"knockout":[159,265],"(KO)":[160],"mice.":[161,298,311,343],"was":[163,200,304,350],"given":[164],"alone":[165],"or":[166,187,237,262,393],"elacridar.":[170],"concentrations":[172],"were":[173,210,223,273,281],"by":[175,231,407],"LC-MS/MS.":[176],"The":[177,299],"(10":[186,329,371],"25":[188,353],"mg/kg/bid":[189],"5":[191],"consecutive":[192],"days)":[193],"TMZ":[197,235,335,349,368,428],"(100":[198],"mg/kg/dayx5)":[199],"studied":[201],"WT":[203,256,297,308,345],"Abcb1/Abcg2":[205],"KO":[206,292,310,342],"recipient":[207],"mice":[208,266,293],"grafted":[211],"intracranially":[212],"derived":[217],"cell":[218],"line.":[219],"Furthermore,":[220],"conducted":[224],"transgenic":[227],"spontaneous":[228],"model":[230],"giving":[232],"without":[238,376],"elacridar":[239,314,364,380],"(50":[240],"bidaily).":[242],"Results:":[243],"AUCs":[244,278],"plasma,":[248],"liver,":[249],"kidney,":[250],"spleen,":[251],"lung":[252],"heart":[254],"vs":[257],"Abcb1,":[259,288],"Abcg2,":[261,289],"Abcb1;Abcg2":[264,291,341],"not":[274,356,389],"different.":[275],"However,":[276],"brains":[280],"4.6,":[282],"1.2":[283],"6.9-fold":[285],"higher":[286],"respectively,":[294],"compared":[295],"oral":[300,394],"bioavailability":[301,395],"also":[305,381],"similar":[306],"Co-administration":[312],"increased":[315],"t-max,":[316],"but":[317,355],"had":[319],"only":[320],"minor":[322],"effect":[323],"plasma":[326],"AUC.":[327],"mg/kg)":[330,372],"potentiated":[331],"against":[336],"implanted":[339],"In":[344],"mice,":[346],"potentiating":[347,427],"seen":[351],"at":[352,357],"mg/kg,":[354],"mg/kg.":[359],"Spontaneous":[360],"tumors":[361],"treated":[362],"responded":[373],"better":[374],"than":[375],"elacridar,":[377],"however,":[378,398],"concomitant":[379],"appeared":[382],"toxicity.":[385],"Conclusions:":[386],"do":[388],"affect":[390],"systemic":[391],"clearance":[392],"ABT-888,":[397],"7-fold":[405],"reduced":[406],"action":[409],"Abcb1":[411],"Abcg2.":[413],"Efficacy":[414],"indicate":[416],"these":[418],"may":[420],"compromise":[421],"effects":[423],"efficacy.":[429],"Citation":[430],"Format:":[431],"{Authors}.":[432],"{Abstract":[433],"title}":[434],"[abstract].":[435],"In:":[436],"Proceedings":[437],"102nd":[440],"Annual":[441],"Meeting":[442],"American":[445],"Association":[446],"Cancer":[448,458],"Research;":[449],"2011":[450],"Apr":[451],"2-6;":[452],"Orlando,":[453],"FL.":[454],"Philadelphia":[455],"(PA):":[456],"AACR;":[457],"Res":[459],"2011;71(8":[460],"Suppl):Abstract":[461],"nr":[462],"LB-210.":[463],"doi:10.1158/1538-7445.AM2011-LB-210":[464]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}