{"id":"https://openalex.org/W2740475656","doi":"https://doi.org/10.1158/1538-7445.am2017-4675","title":"Abstract 4675: Novel combination therapy of DNA methyltransferase inhibitor guadecitabine (SGI-110) and PARP inhibitor talazoparib (BMN-673) for BRCA-proficient high-grade serous ovarian cancer","display_name":"Abstract 4675: Novel combination therapy of DNA methyltransferase inhibitor guadecitabine (SGI-110) and PARP inhibitor talazoparib (BMN-673) for BRCA-proficient high-grade serous ovarian cancer","publication_year":2017,"publication_date":"2017-07-01","ids":{"openalex":"https://openalex.org/W2740475656","doi":"https://doi.org/10.1158/1538-7445.am2017-4675","mag":"2740475656"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2017-4675","doi":"https://doi.org/10.1158/1538-7445.am2017-4675","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2017-4675","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":"https://openalex.org/A5069920578","display_name":"Nicholas Pulliam","orcid":"https://orcid.org/0000-0001-6090-9062","observed_orcids":["https://orcid.org/0000-0001-6090-9062"]},"institutions":[{"id":"https://openalex.org/I4210119109","display_name":"Indiana University Bloomington","ror":"https://ror.org/02k40bc56","country_code":"US","type":"education","lineage":["https://openalex.org/I4210119109","https://openalex.org/I592451"]},{"id":"https://openalex.org/I592451","display_name":"Indiana University","ror":"https://ror.org/01kg8sb98","country_code":"US","type":"education","lineage":["https://openalex.org/I592451"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nicholas Pulliam","raw_affiliation_strings":["1Indiana University, Bloomington, IN;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Indiana University, Bloomington, IN;","institution_ids":["https://openalex.org/I4210119109","https://openalex.org/I592451"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5018689852","display_name":"Pietro Taverna","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4387155454","display_name":"Astex Pharmaceuticals","ror":"https://ror.org/05fx1fs38","country_code":"US","type":"company","lineage":["https://openalex.org/I114030911","https://openalex.org/I4387155454"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Pietro Taverna","raw_affiliation_strings":["2Astex Pharmaceutical, Inc., Pleasanton, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Astex Pharmaceutical, Inc., Pleasanton, CA;","institution_ids":["https://openalex.org/I4387155454"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050224107","display_name":"John F. Lyons","orcid":"https://orcid.org/0009-0002-7080-7937","observed_orcids":["https://orcid.org/0009-0002-7080-7937"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"John Lyons","raw_affiliation_strings":["3Astex Pharmaceutical, Inc., Cambridge, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Astex Pharmaceutical, Inc., Cambridge, United Kingdom","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5061888144","display_name":"Kenneth P. Nephew","orcid":"https://orcid.org/0000-0003-2192-1346","observed_orcids":["https://orcid.org/0000-0003-2192-1346"]},"institutions":[{"id":"https://openalex.org/I4210119109","display_name":"Indiana University Bloomington","ror":"https://ror.org/02k40bc56","country_code":"US","type":"education","lineage":["https://openalex.org/I4210119109","https://openalex.org/I592451"]},{"id":"https://openalex.org/I592451","display_name":"Indiana University","ror":"https://ror.org/01kg8sb98","country_code":"US","type":"education","lineage":["https://openalex.org/I592451"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kenneth P. Nephew","raw_affiliation_strings":["1Indiana University, Bloomington, IN;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Indiana University, Bloomington, IN;","institution_ids":["https://openalex.org/I4210119109","https://openalex.org/I592451"]}]}],"institutions":[],"countries_distinct_count":1,"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":"77","issue":"13_Supplement","first_page":"4675","last_page":"4675"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11914","display_name":"PARP inhibition in cancer therapy","score":0.9994999766349792,"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/T11914","display_name":"PARP inhibition in cancer therapy","score":0.9994999766349792,"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/T10550","display_name":"Ovarian cancer diagnosis and treatment","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/2743","display_name":"Reproductive 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/T10769","display_name":"BRCA gene mutations in cancer","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/guadecitabine","display_name":"guadecitabine","score":0.9900000095367432},{"id":"https://openalex.org/keywords/talazoparib","display_name":"talazoparib","score":0.9300000071525574},{"id":"https://openalex.org/keywords/hypomethylating-agents","display_name":"hypomethylating agents","score":0.7599999904632568},{"id":"https://openalex.org/keywords/parp-inhibitors","display_name":"PARP inhibitors","score":0.984000027179718},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.7020000219345093},{"id":"https://openalex.org/keywords/high-grade-serous-ovarian-carcinoma","display_name":"high-grade serous ovarian cancer","score":0.9950000047683716},{"id":"https://openalex.org/keywords/dna-damage-response","display_name":"DNA damage response","score":0.9169999957084656},{"id":"https://openalex.org/keywords/dna-methylation","display_name":"DNA methylation","score":0.6759999990463257},{"id":"https://openalex.org/keywords/chemoresistance","display_name":"chemoresistance","score":0.6930000185966492},{"id":"https://openalex.org/keywords/platinum-resistance","display_name":"platinum resistance","score":0.7609999775886536},{"id":"https://openalex.org/keywords/brca2-mutation","display_name":"BRCA2 mutation","score":0.8029999732971191},{"id":"https://openalex.org/keywords/dnmt1","display_name":"DNMT1","score":0.8069999814033508},{"id":"https://openalex.org/keywords/dna-repair","display_name":"DNA repair","score":0.4650000035762787},{"id":"https://openalex.org/keywords/ovarian-cancer-cell-lines","display_name":"ovarian cancer cell lines","score":0.5619999766349792}],"concepts":[{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.7103098630905151},{"id":"https://openalex.org/C2779138821","wikidata":"https://www.wikidata.org/wiki/Q7118227","display_name":"PARP inhibitor","level":5,"score":0.7058533430099487},{"id":"https://openalex.org/C2780427987","wikidata":"https://www.wikidata.org/wiki/Q172341","display_name":"Ovarian cancer","level":3,"score":0.6977118849754333},{"id":"https://openalex.org/C2779962180","wikidata":"https://www.wikidata.org/wiki/Q7083106","display_name":"Olaparib","level":5,"score":0.6181631684303284},{"id":"https://openalex.org/C2780194787","wikidata":"https://www.wikidata.org/wiki/Q4836333","display_name":"BRCA mutation","level":4,"score":0.6121817231178284},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5491191148757935},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4947914481163025},{"id":"https://openalex.org/C143425029","wikidata":"https://www.wikidata.org/wiki/Q5205747","display_name":"DNA damage","level":3,"score":0.4719582796096802},{"id":"https://openalex.org/C2779979206","wikidata":"https://www.wikidata.org/wiki/Q1154602","display_name":"DNA methyltransferase","level":5,"score":0.4402436316013336},{"id":"https://openalex.org/C91965660","wikidata":"https://www.wikidata.org/wiki/Q415875","display_name":"Methyltransferase","level":4,"score":0.3593994975090027},{"id":"https://openalex.org/C182979987","wikidata":"https://www.wikidata.org/wiki/Q3907241","display_name":"Poly ADP ribose polymerase","level":4,"score":0.31337034702301025},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.12840715050697327},{"id":"https://openalex.org/C33288867","wikidata":"https://www.wikidata.org/wiki/Q518328","display_name":"Methylation","level":3,"score":0.11088153719902039},{"id":"https://openalex.org/C82381507","wikidata":"https://www.wikidata.org/wiki/Q416878","display_name":"Polymerase","level":3,"score":0.1040421724319458},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.07320931553840637}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2017-4675","doi":"https://doi.org/10.1158/1538-7445.am2017-4675","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2017-4675","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":[{"score":0.98580002784729,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"score":0.8199999928474426,"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/W2562704223","https://openalex.org/W2795391593","https://openalex.org/W4307909225","https://openalex.org/W4403250783","https://openalex.org/W2802835777","https://openalex.org/W2146079836","https://openalex.org/W2955807496","https://openalex.org/W4393088699","https://openalex.org/W2766346630","https://openalex.org/W1967039776"],"abstract_inverted_index":{"Abstract":[0],"Ovarian":[1],"cancer":[2,44,61,100,106,192,339,400],"recurrence":[3],"has":[4],"been":[5],"shown":[6],"to":[7,300,318],"be":[8,24],"associated":[9],"with":[10,139,169,221,258,327],"increased":[11,228,247,282],"DNA":[12,56,66,79,385],"damage":[13,80],"response":[14],"(DDR)":[15],"mediated":[16,62],"by":[17,27,63],"poly-(ADP)-ribose":[18],"polymerase":[19],"1/2":[20],"(PARP1/2),":[21],"which":[22],"can":[23],"therapeutically":[25],"targeted":[26],"PARP":[28,230,254,329,391],"inhibitors":[29],"(PARPi).":[30],"PARPi":[31,90,146],"are":[32],"indicated":[33],"for":[34,55,76,130,367,395,408],"platinum-responsive,":[35],"BRCA-mutated":[36],"high-grade":[37,121,189,336,397],"serous":[38,122,190,337,398],"ovarian":[39,43,60,99,105,191,305,338,399],"cancer,":[40],"but":[41,201],"most":[42],"patients":[45],"have":[46],"BRCA-proficient":[47,396],"disease.":[48],"Our":[49],"previous":[50],"studies":[51],"support":[52],"a":[53,73,87,203,324,328],"role":[54,75],"methylation":[57],"in":[58,78,96,98,151,161,289,332,335],"chemoresistant":[59],"the":[64,198,271,350,405],"enzyme":[65],"methyltransferase":[67,386],"1":[68],"(DNMT1),":[69],"and":[70,89,115,145,251,278,281,297,313,360,390],"report":[71],"on":[72,183,266],"functional":[74],"DNMT1":[77,249],"repair.":[81],"We":[82],"therefore":[83],"hypothesized":[84],"that":[85,349],"combining":[86,167,270,323],"DNMTi":[88,140],"will":[91],"impair":[92],"BRCA-mediated":[93,358],"DDR,":[94],"resulting":[95],"cytotoxicity":[97,334],"cells.":[101],"A":[102],"panel":[103],"of":[104,357,384,404],"cell":[107,131,163,193,267,291,340],"lines":[108,164,194,341],"(A2780,":[109],"platinum":[110,117,124],"sensitive,":[111],"BRCA1/2-wild":[112,119],"type;":[113,120],"A2780-cp":[114],"HeyC2,":[116],"resistant,":[118,125],"Kuramochi,":[123],"BRCA2":[126,210],"mutant)":[127],"was":[128],"examined":[129],"growth":[132],"using":[133],"colony":[134,159],"formation":[135,160],"assays":[136],"after":[137],"treatment":[138,245,365],"guadecitabine":[141,168,223,259,295,388],"(low":[142],"dose,":[143],"20-100nm)":[144],"talazoparib":[147,154,170,244,261,298,393],"(1-10nm),":[148],"alone":[149,155,246,262],"or":[150,206,260,346],"combination.":[152],"While":[153],"only":[156],"marginally":[157],"reduced":[158],"all":[162,176],"(dose-dependent":[165],"effect),":[166],"further":[171],"decreased":[172,252,308],"(P<0.05)":[173,229,248,253],"survival":[174],"at":[175],"doses":[177],"examined.":[178],"To":[179],"focus":[180],"more":[181],"specifically":[182],"BRCA":[184],"status,":[185],"we":[186],"utilized":[187],"two":[188,272],"(\u201cPEO\u201d)":[195],"derived":[196],"from":[197],"same":[199],"patient":[200],"harboring":[202,302,342],"mutant":[204],"(PEO1)":[205],"wild":[207,344],"type":[208,304],"(PEO4)":[209],"gene":[211],"(Langdon":[212],"et":[213,217],"al,":[214,218],"1988;":[215],"Sakai":[216],"2009).":[219],"Treatment":[220,257],"low-dose":[222],"(20":[224],"nm,":[225],"3":[226,287],"days)":[227],"levels":[231,250],"(western":[232],"blot":[233],"analysis)":[234],"as":[235,237],"well":[236],"enzymatic":[238,255],"activity":[239],"(P<0.05;":[240],"ELISA":[241],"analysis),":[242],"while":[243],"activity.":[256],"had":[263],"no":[264],"effect":[265],"proliferation;":[268],"however,":[269],"drugs":[273],"inhibited":[274],"(>80%;":[275],"P<0.05)":[276,284],"PEO1":[277],"PEO4":[279],"proliferation":[280],"(3-fold;":[283],"apoptosis":[285],"(caspase":[286],"cleavage)":[288],"both":[290],"lines.":[292],"Furthermore,":[293],"co-administration":[294],"(0.5mg/kg)":[296],"(0.25mg/kg)":[299],"mice":[301],"BRCA2-wild":[303],"tumor":[306,310,314],"xenografts":[307],"(p<0.05)":[309],"volume":[311],"(>60%)":[312],"weight":[315],"(~70%)":[316],"compared":[317],"control,":[319],"respectively.":[320],"In":[321],"summary,":[322],"hypomethylating":[325],"agent":[326],"inhibitor":[330,387,392],"results":[331],"enhanced":[333],"either":[343],"type-":[345],"mutant-BRCA,":[347],"indicating":[348],"talazoparib-guadecitabine":[351],"drug":[352],"combination":[353,382],"is":[354],"effective":[355,364],"regardless":[356],"DDR":[359],"may":[361],"represent":[362],"an":[363],"regimen":[366],"BRCA-related":[368],"cancers.":[369],"Citation":[370],"Format:":[371],"Nicholas":[372],"Pulliam,":[373],"Pietro":[374],"Taverna,":[375],"John":[376],"Lyons,":[377],"Kenneth":[378],"P.":[379],"Nephew.":[380],"Novel":[381],"therapy":[383],"(SGI-110)":[389],"(BMN-673)":[394],"[abstract].":[401],"In:":[402],"Proceedings":[403],"American":[406],"Association":[407],"Cancer":[409,422],"Research":[410],"Annual":[411],"Meeting":[412],"2017;":[413],"2017":[414],"Apr":[415],"1-5;":[416],"Washington,":[417],"DC.":[418],"Philadelphia":[419],"(PA):":[420],"AACR;":[421],"Res":[423],"2017;77(13":[424],"Suppl):Abstract":[425],"nr":[426],"4675.":[427],"doi:10.1158/1538-7445.AM2017-4675":[428]},"counts_by_year":[],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2017-08-08T00:00:00"}
