{"id":"https://openalex.org/W2333558353","doi":"https://doi.org/10.1158/1538-7445.am2012-1461","title":"Abstract 1461: MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation","display_name":"Abstract 1461: MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation","publication_year":2012,"publication_date":"2012-04-01","ids":{"openalex":"https://openalex.org/W2333558353","doi":"https://doi.org/10.1158/1538-7445.am2012-1461","mag":"2333558353"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2012-1461","doi":"https://doi.org/10.1158/1538-7445.am2012-1461","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2012-1461","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","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":null,"display_name":"Li Wang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Li Wang","raw_affiliation_strings":["1UT MD Anderson Cancer Ctr., Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Ctr., Houston, TX","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110489116","display_name":"Kathy A. Mason","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kathy A. Mason","raw_affiliation_strings":["1UT MD Anderson Cancer Ctr., Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Ctr., Houston, TX","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108207574","display_name":"K. Kian Ang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"K. Kian Ang","raw_affiliation_strings":["1UT MD Anderson Cancer Ctr., Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Ctr., Houston, TX","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045529171","display_name":"Thomas A. Buchholz","orcid":"https://orcid.org/0000-0002-7859-5572","observed_orcids":["https://orcid.org/0000-0002-7859-5572"]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Thomas Buchholz","raw_affiliation_strings":["1UT MD Anderson Cancer Ctr., Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Ctr., Houston, TX","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110120167","display_name":"David R. Valdecanas","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Valdecanas","raw_affiliation_strings":["1UT MD Anderson Cancer Ctr., Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Ctr., Houston, TX","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057687644","display_name":"Anjili Mathur","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Anjili Mathur","raw_affiliation_strings":["2Merck Research Labs, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Merck Research Labs, Boston, MA","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061571393","display_name":"Carolyn Buser\u2010Doepner","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Carolyn Buser-Doepner","raw_affiliation_strings":["2Merck Research Labs, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Merck Research Labs, Boston, MA","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015441971","display_name":"Carlo Toniatti","orcid":"https://orcid.org/0000-0001-9493-344X","observed_orcids":["https://orcid.org/0000-0001-9493-344X"]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Carlo Toniatti","raw_affiliation_strings":["2Merck Research Labs, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Merck Research Labs, Boston, MA","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5108796110","display_name":"Luka Milas","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Luka Milas","raw_affiliation_strings":["1UT MD Anderson Cancer Ctr., Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Ctr., Houston, TX","institution_ids":["https://openalex.org/I1343551460"]}]}],"institutions":[],"countries_distinct_count":1,"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":"72","issue":"8_Supplement","first_page":"1461","last_page":"1461"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11914","display_name":"PARP inhibition in cancer therapy","score":0.9990000128746033,"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":0.9990000128746033,"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/T11359","display_name":"Effects of Radiation Exposure","score":0.00039999998989515007,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"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/T11176","display_name":"Radiation Therapy and Dosimetry","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/3108","display_name":"Radiation"},"field":{"id":"https://openalex.org/fields/31","display_name":"Physics and Astronomy"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/parp1-inhibitors","display_name":"PARP-1 inhibitors","score":0.8240000009536743},{"id":"https://openalex.org/keywords/radiosensitization","display_name":"radiosensitization","score":0.9300000071525574},{"id":"https://openalex.org/keywords/radiotherapy","display_name":"radiotherapy","score":0.4269999861717224},{"id":"https://openalex.org/keywords/lung-cancer-xenografts","display_name":"lung cancer xenografts","score":0.8690000176429749},{"id":"https://openalex.org/keywords/breast-cancer-xenografts","display_name":"breast cancer xenografts","score":0.9900000095367432},{"id":"https://openalex.org/keywords/tp53-status","display_name":"p53 status","score":0.8569999933242798},{"id":"https://openalex.org/keywords/fractionated-x-ray-irradiation","display_name":"fractionated X-ray irradiation","score":0.8309999704360962},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.5950000286102295},{"id":"https://openalex.org/keywords/triple-negative-breast-cancer","display_name":"triple-negative breast cancer","score":0.6809999942779541},{"id":"https://openalex.org/keywords/a549-cells","display_name":"A549 cells","score":0.9110000133514404},{"id":"https://openalex.org/keywords/mda-mb-231-cells","display_name":"MDA-MB-231 cells","score":0.9470000267028809},{"id":"https://openalex.org/keywords/tumor-growth-inhibition","display_name":"tumor growth inhibition","score":0.8149999976158142}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6377965211868286},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5517666935920715},{"id":"https://openalex.org/C2779138821","wikidata":"https://www.wikidata.org/wiki/Q7118227","display_name":"PARP inhibitor","level":5,"score":0.5487167239189148},{"id":"https://openalex.org/C509974204","wikidata":"https://www.wikidata.org/wiki/Q180507","display_name":"Radiation therapy","level":2,"score":0.4512929916381836},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.42231595516204834},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.36538150906562805},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.32535621523857117},{"id":"https://openalex.org/C182979987","wikidata":"https://www.wikidata.org/wiki/Q3907241","display_name":"Poly ADP ribose polymerase","level":4,"score":0.3150980472564697},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.24988943338394165},{"id":"https://openalex.org/C82381507","wikidata":"https://www.wikidata.org/wiki/Q416878","display_name":"Polymerase","level":3,"score":0.10719022154808044},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2012-1461","doi":"https://doi.org/10.1158/1538-7445.am2012-1461","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2012-1461","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":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.98580002784729}],"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/W2050050592","https://openalex.org/W1922143413","https://openalex.org/W2145687970","https://openalex.org/W2590906432","https://openalex.org/W2324263748","https://openalex.org/W2042251066","https://openalex.org/W2171474267","https://openalex.org/W4249199995","https://openalex.org/W2590549628","https://openalex.org/W2140010849"],"abstract_inverted_index":{"Abstract":[0],"The":[1,489],"poly-(ADP-ribose)":[2],"polymerase":[3],"(PARP)":[4],"inhibitor,":[5],"MK-4827,":[6,168,245,271],"is":[7],"a":[8,46,285,439,479],"novel":[9],"potent,":[10],"orally":[11],"bioavailable":[12],"PARP-1":[13],"and":[14,67,71,228,263,294,316,330,350,357,369,391,445],"PARP-2":[15],"inhibitor":[16],"currently":[17,29],"in":[18,84,114,401,455],"phase":[19],"I":[20],"clinical":[21,500],"trials":[22],"for":[23,108,181,209,221,229,241,249,270,347,375,387,398,449,464,520],"cancer":[24,58],"treatment.":[25],"No":[26],"preclinical":[27],"data":[28],"exist":[30],"on":[31,206,478],"the":[32,85,140,153,192,212,317,413,430,474,512,517],"combination":[33,416],"of":[34,45,48,52,88,139,152,211,239,287,307,344,415,432,442,476,481,486,511,516],"MK-4827":[35,42,126,173,201,281,295,299,309,333,336,402,435,451,471],"with":[36,244],"radiotherapy":[37],"(XRT).":[38],"We":[39],"examined":[40],"whether":[41],"enhances":[43],"radiosensitivity":[44],"variety":[47,480],"human":[49,75,409,482],"tumor":[50,207,427,483],"xenografts":[51,78,82,219,352,400,484],"differing":[53],"p53":[54,216,322,487],"status.":[55,488],"Human":[56],"lung":[57],"xenografts,":[59,326,412],"Calu-6":[60,218],"(p53":[61,64,69],"null),":[62],"A549":[63,399],"wild-type":[65],"[wt])":[66],"H-460":[68],"wt)":[70],"triple":[72],"negative":[73],"MDA-MB-231":[74,408],"breast":[76,410],"carcinoma":[77,411],"were":[79,91,158,379,447],"used.":[80,335],"Tumor":[81,176],"growing":[83],"hind":[86],"leg":[87],"nude":[89],"mice":[90],"exposed":[92],"to":[93,183,188,256,312,382,466,498],"fractionated":[94],"XRT":[95,101,138,151,170,232,240,293,329,404,421],"at":[96,284],"8":[97],"mm":[98,160,187],"(diameter).":[99],"Fractionated":[100],"(2":[102],"Gy":[103],"per":[104],"fraction)":[105],"was":[106,127,191,198,224,233,278,282,300,310,319,334,337,353,365,418,436],"delivered":[107],"7":[109,242],"(twice":[110],"daily,":[111,298],"6":[112,159],"h":[113,135,148,459],"between)":[115],"or":[116,142,171],"14":[117],"(once":[118],"daily)":[119],"consecutive":[120,251],"days,":[121,252],"total":[122],"dose":[123,286,441],"28":[124],"Gy.":[125],"given":[128,283,296,437],"by":[129,457],"gavage":[130],"once":[131,273,290,297,331],"(50":[132],"mg/kg,":[133,146],"1":[134,147,458],"before":[136,149],"first":[137],"day)":[141,154],"twice":[143,230,247,327],"daily":[144,231,248,328,332],"(25":[145],"each":[150],"starting":[155],"when":[156,280],"tumors":[157,182,213,223,446,456],"diameter.":[161],"Mice":[162],"received":[163],"(a)":[164],"no":[165,204,425],"treatment,":[166],"(b)":[167],"(c)":[169],"(d)":[172],"plus":[174,403],"XRT.":[175,345],"growth":[177,208],"delay":[178],"(TGD,":[179],"days":[180,243,260,267,304,341,361,373,386,395],"grow":[184],"from":[185],"8.0":[186],"12.0":[189],"mm)":[190],"endpoint.":[193],"Radiation":[194],"enhancement":[195,277],"factor":[196],"(EF)":[197],"then":[199],"calculated.":[200],"alone":[202,422],"had":[203],"effect":[205,475],"any":[210],"types.":[214],"For":[215,292,321],"mutant":[217],"TGD":[220,255,346],"untreated":[222,348],"13.2":[225],"\u00b1":[226,235,258,265,355,359,367,371,384,393],"0.5":[227,356,368],"30.9":[234],"2.4":[236],"days.":[237],"Combination":[238],"25mg/kg":[246],"21":[250],"further":[253,380],"extended":[254,381],"39.7":[257],"2.0":[259],"(EF":[261,268,389,396],"1.4)":[262],"47.8":[264],"4.0":[266],"2.03)":[269],"50mg/kg":[272],"daily.":[274,291],"Maximum":[275],"radiation":[276,477],"observed":[279],"50":[288,443],"mg/kg":[289,444],"continued":[301,338],"until":[302,339,429],"2":[303,340],"after":[305,342,460],"completion":[306,343],"XRT,":[308],"found":[311],"be":[313],"similarly":[314],"effective":[315],"EF":[318],"1.7.":[320],"wt":[323],"H460and":[324],"A459":[325,351],"H460":[349,388],"7.8":[354],"33.2":[358],"1.5":[360],"respectively;":[362],"whereas":[363],"it":[364],"15.6":[366],"53.2":[370],"3.1":[372],"respectively":[374],"irradiated":[376],"tumors.":[377],"TGDs":[378],"26.0":[383],"3.5":[385],"2.2)":[390],"64.1":[392],"4.2":[394],"1.9)":[397],"groups.":[405],"Similarly,":[406],"using":[407],"potency":[414],"treatment":[417],"greater":[419],"than":[420],"showing":[423],"essentially":[424],"local":[426],"regrowth":[428],"occurrence":[431],"metastases.":[433],"When":[434],"as":[438],"single":[440],"assayed":[448],"PAR,":[450],"reduced":[452],"PAR":[453],"levels":[454],"administration":[461],"which":[462],"persisted":[463],"up":[465],"24":[467],"h.":[468],"In":[469],"conclusion,":[470],"strongly":[472],"enhanced":[473],"irrespective":[485],"long":[490],"lasting":[491],"PARP":[492],"inhibition":[493],"(1-24h)":[494],"potentially":[495],"adds":[496],"flexibility":[497],"future":[499],"trial":[501],"design.":[502],"Citation":[503],"Format:":[504],"{Authors}.":[505],"{Abstract":[506],"title}":[507],"[abstract].":[508],"In:":[509],"Proceedings":[510],"103rd":[513],"Annual":[514],"Meeting":[515],"American":[518],"Association":[519],"Cancer":[521,532],"Research;":[522],"2012":[523],"Mar":[524],"31-Apr":[525],"4;":[526],"Chicago,":[527],"IL.":[528],"Philadelphia":[529],"(PA):":[530],"AACR;":[531],"Res":[533],"2012;72(8":[534],"Suppl):Abstract":[535],"nr":[536],"1461.":[537],"doi:1538-7445.AM2012-1461":[538]},"counts_by_year":[],"updated_date":"2026-10-11T09:32:39.932853","created_date":"2016-06-24T00:00:00"}