{"id":"https://openalex.org/W4390730685","doi":"https://doi.org/10.1158/1538-7445.dnarepair24-ia008","title":"Abstract IA008: Targeting homologous recombination deficiency (HRD) using optimized ionizing radiation and drug combinations","display_name":"Abstract IA008: Targeting homologous recombination deficiency (HRD) using optimized ionizing radiation and drug combinations","publication_year":2024,"publication_date":"2024-01-09","ids":{"openalex":"https://openalex.org/W4390730685","doi":"https://doi.org/10.1158/1538-7445.dnarepair24-ia008"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.dnarepair24-ia008","doi":"https://doi.org/10.1158/1538-7445.dnarepair24-ia008","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.dnarepair24-ia008","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/A5056895130","display_name":"Simon N. Powell","orcid":"https://orcid.org/0000-0002-8183-4765","observed_orcids":["https://orcid.org/0000-0002-8183-4765"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Simon N. Powell","raw_affiliation_strings":["1Memorial Sloan Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079128655","display_name":"Niamh McDermott","orcid":"https://orcid.org/0000-0001-6045-9364","observed_orcids":["https://orcid.org/0000-0001-6045-9364"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Niamh McDermott","raw_affiliation_strings":["1Memorial Sloan Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5113092679","display_name":"Robert Delsite","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Robert Delsite","raw_affiliation_strings":["1Memorial Sloan Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1334819555"],"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":"84","issue":"1_Supplement","first_page":"IA008","last_page":"IA008"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11914","display_name":"PARP inhibition in cancer therapy","score":0.9922000169754028,"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":0.9922000169754028,"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/T10769","display_name":"BRCA gene mutations in cancer","score":0.0035000001080334187,"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"}},{"id":"https://openalex.org/T10123","display_name":"DNA Repair Mechanisms","score":0.0017999999690800905,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/homologous-recombination-deficiency","display_name":"homologous recombination deficiency","score":1.0},{"id":"https://openalex.org/keywords/triple-negative-breast-cancer","display_name":"triple-negative breast cancer","score":0.9110000133514404},{"id":"https://openalex.org/keywords/radiotherapy","display_name":"radiotherapy","score":0.597000002861023},{"id":"https://openalex.org/keywords/parp-inhibitors","display_name":"PARP inhibitors","score":0.8050000071525574},{"id":"https://openalex.org/keywords/talazoparib","display_name":"talazoparib","score":0.9829999804496765},{"id":"https://openalex.org/keywords/cisplatin","display_name":"cisplatin","score":0.8669999837875366},{"id":"https://openalex.org/keywords/radiosensitization","display_name":"radiosensitization","score":0.9810000061988831},{"id":"https://openalex.org/keywords/nad-depletion","display_name":"NAD+ depletion","score":0.9330000281333923},{"id":"https://openalex.org/keywords/parthanatos","display_name":"parthanatos","score":0.9070000052452087},{"id":"https://openalex.org/keywords/poly-adp-ribosyl-ation","display_name":"poly(ADP-ribosyl)ation","score":0.4449999928474426},{"id":"https://openalex.org/keywords/rad51-foci","display_name":"RAD51 foci","score":0.8389999866485596},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.4729999899864197},{"id":"https://openalex.org/keywords/maximum-tolerated-dose","display_name":"maximum tolerated dose","score":0.5730000138282776}],"concepts":[{"id":"https://openalex.org/C2779012473","wikidata":"https://www.wikidata.org/wiki/Q3235015","display_name":"RAD51","level":4,"score":0.8230773210525513},{"id":"https://openalex.org/C2779138821","wikidata":"https://www.wikidata.org/wiki/Q7118227","display_name":"PARP inhibitor","level":5,"score":0.7297863364219666},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5960864424705505},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5471913814544678},{"id":"https://openalex.org/C509974204","wikidata":"https://www.wikidata.org/wiki/Q180507","display_name":"Radiation therapy","level":2,"score":0.4875640273094177},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.48602229356765747},{"id":"https://openalex.org/C102744134","wikidata":"https://www.wikidata.org/wiki/Q22280388","display_name":"Homologous recombination","level":3,"score":0.48515185713768005},{"id":"https://openalex.org/C18231593","wikidata":"https://www.wikidata.org/wiki/Q186161","display_name":"Ionizing radiation","level":3,"score":0.4202568531036377},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.34805673360824585},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3295939862728119},{"id":"https://openalex.org/C182979987","wikidata":"https://www.wikidata.org/wiki/Q3907241","display_name":"Poly ADP ribose polymerase","level":4,"score":0.2520586848258972},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.20879867672920227},{"id":"https://openalex.org/C111337013","wikidata":"https://www.wikidata.org/wiki/Q2737837","display_name":"Irradiation","level":2,"score":0.17743739485740662},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.14717641472816467},{"id":"https://openalex.org/C185544564","wikidata":"https://www.wikidata.org/wiki/Q81197","display_name":"Nuclear physics","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},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.dnarepair24-ia008","doi":"https://doi.org/10.1158/1538-7445.dnarepair24-ia008","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.dnarepair24-ia008","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":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/W7129353819","https://openalex.org/W4400571205","https://openalex.org/W2741976753","https://openalex.org/W2759043275","https://openalex.org/W1613365595","https://openalex.org/W2295085830","https://openalex.org/W2779333875","https://openalex.org/W4410475750","https://openalex.org/W3108286628","https://openalex.org/W2759863599"],"abstract_inverted_index":{"Abstract":[0],"Homologous":[1],"recombination":[2,424],"deficiency":[3,425],"(HRD)":[4,426],"is":[5,17,35,81,229,249,254,294,314,353],"found":[6],"not":[7,282,324],"only":[8,167],"in":[9,20,42,59,138,161,168,187,267,278,291,305,363,442],"germline":[10],"mutation":[11],"carriers":[12],"of":[13,26,33,88,94,104,111,131,153,182,212,220,235,247,264,285,288,300,311,319,335,349,361,366,369,379,395,408,437],"HR":[14,28,50,71],"genes":[15],"but":[16,166,330],"also":[18],"observed":[19,208,355],"sporadic":[21],"cancers":[22],"when":[23,244],"both":[24],"copies":[25],"the":[27,70,109,122,150,180,183,210,216,245,258,286,316,326,336,343,357,364,380,385,393,438],"gene":[29,46],"are":[30,65,224],"inactivated.":[31],"Recognition":[32],"HRD":[34,85,127,139,164,199,268,292,409],"facilitated":[36],"by":[37,55,178,209,375],"using":[38,427],"genomic":[39],"landscape":[40],"alterations":[41],"addition":[43],"to":[44,68,120,126,141,239,262,338,372,383,397,451],"target":[45],"sequencing.":[47],"In":[48,100,149],"addition,":[49],"function":[51,73],"can":[52],"be":[53,142,325,373,390,411],"established":[54],"measuring":[56],"RAD51":[57],"foci":[58],"tumor":[60],"specimens,":[61],"particularly":[62,304],"if":[63],"they":[64],"irradiated":[66],"ex-vivo":[67],"reveal":[69],"pathway":[72],"more":[74,143],"clearly.":[75],"Triple":[76],"negative":[77],"breast":[78],"cancer":[79],"(TNBC)":[80],"highly":[82],"enriched":[83],"for":[84,272,345],"constituting":[86],"~45%":[87],"primary":[89],"tumors":[90],"and":[91,237,431],"over":[92],"50%":[93],"locally":[95],"recurrent":[96,105],"or":[97],"metastatic":[98],"cancers.":[99],"a":[101,332],"clinical":[102,123,151,190],"trial":[103,191],"TNBC,":[106],"we":[107],"used":[108],"combination":[110,130,181,259,318,337,381],"ionizing":[112,429],"radiation":[113,402,430],"(IR)":[114],"with":[115,185,195,226,307,321,404],"low-dose":[116],"weekly":[117],"cisplatin":[118],"(cis)":[119],"study":[121,152,177],"response":[124],"according":[125],"status.":[128],"The":[129,270,309],"IR":[132,236,370],"+":[133],"cis":[134],"has":[135],"been":[136],"shown":[137],"cells":[140,200,280,293],"sensitizing":[144],"than":[145],"either":[146],"agent":[147],"alone.":[148],"49":[154],"TNBC":[155],"patients,":[156,165],"there":[157,228,253],"were":[158],"imaging":[159],"responses":[160],"22/29":[162],"(75%)":[163],"4/20":[169],"(20%)":[170],"HR-proficient":[171,279],"patients.":[172],"We":[173],"have":[174,201,371],"followed":[175],"this":[176,274,312,399],"investigating":[179],"PARP-inhibitor":[184,322,346,362],"radiotherapy":[186,320],"an":[188],"ongoing":[189],"as":[192,194,207],"well":[193],"detailed":[196],"cell-based":[197],"studies.":[198],"elevated":[202],"PARP":[203],"activity":[204],"at":[205,233],"baseline,":[206],"extent":[211],"PARylated":[213],"proteins,":[214],"plus":[215],"lower":[217],"baseline":[218],"levels":[219],"NAD.":[221],"When":[222],"PARP-inhibitors":[223],"combined":[225],"radiotherapy,":[227],"demonstrable":[230],"supra-additive":[231],"sensitization":[232],"6Gy":[234],"up":[238],"100nM":[240],"talazoparib":[241],"(TZ).":[242],"However,":[243],"dose":[246,360],"TZ":[248,301],"above":[250],"1":[251],"\u00b5M,":[252],"paradoxical":[255,275],"recovery":[256,276],"from":[257],"therapy,":[260],"due":[261],"rescue":[263],"NAD":[265],"depletion":[266],"cells.":[269],"threshold":[271,344],"seeing":[273],"effect":[277],"was":[281],"reached.":[283],"One":[284],"mechanisms":[287],"cell":[289,350],"killing":[290],"enhanced":[295],"parthanatos,":[296],"which":[297],"higher":[298],"doses":[299,368],"will":[302,389,410],"prevent,":[303],"conjunction":[306],"IR.":[308],"implication":[310],"work":[313],"that":[315,356],"optimal":[317],"may":[323],"maximum":[327,358],"tolerated":[328,359],"dose,":[329],"rather":[331],"tuned":[333],"level":[334],"maximize":[339],"radiosensitization":[340],"without":[341],"exceeding":[342],"mediated":[347],"protection":[348],"death.":[351],"It":[352],"already":[354],"setting":[365],"curative":[367],"modified":[374],"3-10-fold.":[376],"Further":[377],"optimization":[378],"dosing":[382],"achieve":[384,398],"maximal":[386],"therapeutic":[387],"ratio":[388],"discussed":[391],"including":[392],"development":[394],"biomarkers":[396],"goal.":[400],"Additional":[401],"combinations":[403,433],"synthetic":[405],"lethal":[406],"targets":[407],"discussed.":[412],"Citation":[413],"Format:":[414],"Simon":[415],"N.":[416],"Powell,":[417],"Niamh":[418],"McDermott,":[419],"Robert":[420],"Delsite.":[421],"Targeting":[422],"homologous":[423],"optimized":[428],"drug":[432],"[abstract].":[434],"In:":[435],"Proceedings":[436],"AACR":[439],"Special":[440],"Conference":[441],"Cancer":[443,463],"Research:":[444],"DNA":[445],"Damage":[446],"Repair:":[447],"From":[448],"Basic":[449],"Science":[450],"Future":[452],"Clinical":[453],"Application;":[454],"2024":[455],"Jan":[456],"9-11;":[457],"Washington,":[458],"DC.":[459],"Philadelphia":[460],"(PA):":[461],"AACR;":[462],"Res":[464],"2024;84(1":[465],"Suppl):Abstract":[466],"nr":[467],"IA008.":[468]},"counts_by_year":[],"updated_date":"2026-07-14T23:27:15.235271","created_date":"2024-01-13T00:00:00"}
