{"id":"https://openalex.org/W4393085997","doi":"https://doi.org/10.1158/1538-7445.am2024-2866","title":"Abstract 2866: NAPRTsilencing in rhabdomyosarcoma confers therapeutic vulnerabilities to NAD+depletion","display_name":"Abstract 2866: NAPRTsilencing in rhabdomyosarcoma confers therapeutic vulnerabilities to NAD+depletion","publication_year":2024,"publication_date":"2024-03-22","ids":{"openalex":"https://openalex.org/W4393085997","doi":"https://doi.org/10.1158/1538-7445.am2024-2866"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2024-2866","doi":"https://doi.org/10.1158/1538-7445.am2024-2866","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.am2024-2866","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/A5101321892","display_name":"Sophia J. Zhao","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sophia J. Zhao","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066784825","display_name":"Katelyn J. Noronha","orcid":"https://orcid.org/0000-0003-1994-2754","observed_orcids":["https://orcid.org/0000-0003-1994-2754"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Katelyn J. Noronha","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5078830681","display_name":"Prateek Bhardwaj","orcid":"https://orcid.org/0000-0001-5546-7829","observed_orcids":["https://orcid.org/0000-0001-5546-7829"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Prateek Bhardwaj","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113273006","display_name":"Karlie N. Lucas","orcid":"https://orcid.org/0009-0001-0520-186X","observed_orcids":["https://orcid.org/0009-0001-0520-186X"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Karlie N. Lucas","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5016318219","display_name":"Ranjini K. Sundaram","orcid":"https://orcid.org/0000-0002-5725-0284","observed_orcids":["https://orcid.org/0000-0002-5725-0284"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ranjini K. Sundaram","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013489966","display_name":"Collin D. Heer","orcid":"https://orcid.org/0000-0002-9005-3979","observed_orcids":["https://orcid.org/0000-0002-9005-3979"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Collin D. Heer","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5080694430","display_name":"Raffaella A. Morotti","orcid":"https://orcid.org/0000-0002-7863-1772","observed_orcids":["https://orcid.org/0000-0002-7863-1772"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Raffaella Morotti","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5030811047","display_name":"Joshua M. Spurrier","orcid":"https://orcid.org/0000-0002-6267-7231","observed_orcids":["https://orcid.org/0000-0002-6267-7231"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Josh Spurrier","raw_affiliation_strings":["2Alphina Therapeutics, New Haven, CT"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Alphina Therapeutics, New Haven, CT","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5018531947","display_name":"Mitch Raponi","orcid":"https://orcid.org/0009-0004-1838-7765","observed_orcids":["https://orcid.org/0009-0004-1838-7765"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mitch Raponi","raw_affiliation_strings":["2Alphina Therapeutics, New Haven, CT"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Alphina Therapeutics, New Haven, CT","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040738951","display_name":"Ranjit S. Bindra","orcid":"https://orcid.org/0000-0002-3255-0467","observed_orcids":["https://orcid.org/0000-0002-3255-0467"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ranjit S. Bindra","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5062737849","display_name":"Juan C. Vasquez","orcid":"https://orcid.org/0000-0002-9031-7639","observed_orcids":["https://orcid.org/0000-0002-9031-7639"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Juan C. Vasquez","raw_affiliation_strings":["1Yale School of Medicine, New Haven, CT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Yale School of Medicine, New Haven, CT;","institution_ids":["https://openalex.org/I32971472"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"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":"84","issue":"6_Supplement","first_page":"2866","last_page":"2866"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11051","display_name":"Sirtuins and Resveratrol in Medicine","score":0.73580002784729,"subfield":{"id":"https://openalex.org/subfields/2717","display_name":"Geriatrics and Gerontology"},"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/T11051","display_name":"Sirtuins and Resveratrol in Medicine","score":0.73580002784729,"subfield":{"id":"https://openalex.org/subfields/2717","display_name":"Geriatrics and Gerontology"},"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/T10253","display_name":"Sarcoma Diagnosis and Treatment","score":0.1281999945640564,"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/T12827","display_name":"Biochemical and Molecular Research","score":0.0333000011742115,"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/rhabdomyosarcoma","display_name":"rhabdomyosarcoma","score":0.9980000257492065},{"id":"https://openalex.org/keywords/nicotinate-phosphoribosyltransferase","display_name":"NAPRT","score":0.847000002861023},{"id":"https://openalex.org/keywords/visfatin","display_name":"visfatin","score":0.9279999732971191},{"id":"https://openalex.org/keywords/nampt-inhibitors","display_name":"NAMPT inhibitors","score":0.9800000190734863},{"id":"https://openalex.org/keywords/nad-depletion","display_name":"NAD+ depletion","score":0.9240000247955322},{"id":"https://openalex.org/keywords/synthetic-lethality","display_name":"synthetic lethality","score":0.9079999923706055},{"id":"https://openalex.org/keywords/promoter-hypermethylation","display_name":"promoter hypermethylation","score":0.8629999756813049},{"id":"https://openalex.org/keywords/cpg-island-methylation","display_name":"CpG island methylation","score":0.8370000123977661},{"id":"https://openalex.org/keywords/nad-salvage-pathway","display_name":"NAD+ salvage pathway","score":0.7139999866485596},{"id":"https://openalex.org/keywords/therapeutic-biomarkers","display_name":"therapeutic biomarkers","score":0.5630000233650208},{"id":"https://openalex.org/keywords/tumor-regression","display_name":"tumor regression","score":0.36899998784065247},{"id":"https://openalex.org/keywords/pediatric-soft-tissue-sarcoma","display_name":"pediatric soft tissue sarcoma","score":0.7829999923706055}],"concepts":[{"id":"https://openalex.org/C75520062","wikidata":"https://www.wikidata.org/wiki/Q15321392","display_name":"NAD+ kinase","level":3,"score":0.5346466898918152},{"id":"https://openalex.org/C119056186","wikidata":"https://www.wikidata.org/wiki/Q1431332","display_name":"Gene silencing","level":3,"score":0.44818827509880066},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.4165884852409363},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3577662408351898},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3538628816604614},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.16272324323654175},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.16049820184707642},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.13593748211860657},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.056476205587387085}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2024-2866","doi":"https://doi.org/10.1158/1538-7445.am2024-2866","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.am2024-2866","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","score":0.98580002784729,"id":"https://metadata.un.org/sdg/3"}],"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/W4402266832","https://openalex.org/W4412798190","https://openalex.org/W4409640687","https://openalex.org/W4362594832","https://openalex.org/W4409636620","https://openalex.org/W7214043973","https://openalex.org/W4281645694","https://openalex.org/W4241024568","https://openalex.org/W7148887453","https://openalex.org/W7149010655"],"abstract_inverted_index":{"Abstract":[0],"Rhabdomyosarcoma":[1],"(RMS)":[2],"is":[3],"the":[4,28,80,143,167,196,237,272,325,336,339,352,411],"most":[5],"common":[6],"soft":[7],"tissue":[8],"sarcoma":[9],"among":[10],"children,":[11],"and":[12,30,39,68,76,148,278,360],"new":[13],"treatments":[14],"are":[15,189],"needed":[16],"to":[17,113,123,192,211,405],"improve":[18],"survival.":[19],"Cells":[20],"primarily":[21],"synthesize":[22],"nicotinamide":[23,40],"adenine":[24],"dinucleotide":[25],"(NAD)":[26],"through":[27],"Preiss-Handler":[29],"Salvage":[31],"pathways":[32],"driven":[33],"by":[34,59,100,170,216,306],"nicotinic":[35,199],"acid":[36,200],"phosphoribosyltransferase":[37,41],"(NAPRT)":[38],"(NAMPT),":[42],"respectively.":[43],"NAMPT":[44],"inhibitors":[45],"(NAMPTi)":[46],"have":[47],"been":[48,57,83],"tested":[49],"in":[50,86,115,158,173,195,218,228,243,304,318,345,364,400],"clinical":[51,343],"trials,":[52],"but":[53],"their":[54],"efficacy":[55,353],"has":[56,82],"limited":[58],"(a)":[60],"lack":[61],"of":[62,97,118,153,176,198,246,274,282,287,328,341,354,410],"appropriate":[63],"biomarkers":[64],"for":[65,111,271,338,414],"patient":[66],"selection,":[67],"(b)":[69],"significant":[70,225],"dose-limiting":[71],"toxicities":[72],"(DLTs),":[73],"including":[74],"myelosuppression":[75],"retinal":[77],"toxicity,":[78],"although":[79],"latter":[81],"described":[84],"only":[85],"preclinical":[87],"studies.":[88],"Previous":[89],"work":[90],"from":[91],"our":[92],"group":[93],"indicates":[94],"that":[95,130,186,295,331],"loss":[96,286,297],"NAPRT":[98,128,154,162,240,260,288,296,329],"expression":[99,242,330],"tumor-specific":[101],"promoter":[102,156],"CpG":[103],"island":[104],"methylation":[105,140],"may":[106,298],"provide":[107],"a":[108,116,132,150,174,229,244,257,266,301,308],"novel":[109],"biomarker":[110],"sensitivity":[112,210],"NAMPTi":[114,193,212,223,333,356],"variety":[117],"tumors.":[119,367],"Here,":[120],"we":[121],"sought":[122],"determine":[124,324],"if":[125],"RMS":[126,159,177,231,249,283,305],"harbors":[127],"silencing":[129,163],"confers":[131,402],"synthetic":[133,309],"lethal":[134,310],"interaction":[135,311],"with":[136,312,357],"NAMPTi.":[137],"We":[138],"probed":[139],"data":[141,293],"within":[142],"Cancer":[144,415,433],"Dependency":[145],"Map":[146],"(DepMap)":[147],"found":[149],"high":[151],"frequency":[152],"gene":[155],"hypermethylation":[157],"models.":[160],"Predicted":[161],"was":[164,213,251],"confirmed":[165],"at":[166],"protein":[168,241,289],"level":[169],"western":[171],"blot":[172],"panel":[175],"cell":[178],"lines.":[179],"In":[180,221],"vitro":[181],"growth":[182],"delay":[183],"assays":[184],"demonstrated":[185,285],"NAPRT-silenced":[187,230],"cells":[188,205,277],"exquisitely":[190],"sensitive":[191],"even":[194],"presence":[197],"(NA)":[201],"supplementation,":[202],"while":[203],"NAPRT-expressing":[204],"were":[206],"completely":[207],"rescued.":[208],"This":[209],"further":[214,235],"mirrored":[215],"changes":[217],"NAD":[219],"levels.":[220],"vivo,":[222],"induced":[224],"tumor":[226,276],"regression":[227],"xenograft":[232,320],"model.":[233],"To":[234],"establish":[236],"translational":[238],"relevance,":[239],"TMA":[245],"51":[247],"human":[248],"tumors":[250],"assessed":[252],"via":[253],"IHC":[254],"staining":[255,279],"using":[256],"newly":[258],"validated":[259],"monoclonal":[261],"antibody":[262],"(4A5D7).":[263],"Based":[264],"on":[265],"semi-quantitative":[267],"scoring":[268],"system":[269],"accounting":[270],"percentage":[273],"positive":[275],"intensity,":[280],"28%":[281],"samples":[284],"expression.":[290],"Overall,":[291],"these":[292,365],"suggest":[294],"serve":[299],"as":[300],"therapeutic":[302,403],"target":[303],"inducing":[307],"NAD+":[313],"depleting":[314],"agents.":[315],"Future":[316],"studies":[317,348],"patient-derived":[319],"(PDX)":[321],"models":[322],"will":[323,349],"optimal":[326],"cut-off":[327],"portends":[332],"sensitivity,":[334],"paving":[335],"way":[337],"development":[340],"biomarker-driven":[342],"trials":[344],"RMS.":[346],"Ongoing":[347],"also":[350],"evaluate":[351],"combining":[355],"existing":[358],"cytotoxic":[359],"DNA":[361],"damaging":[362],"chemotherapy":[363],"difficult-to-treat":[366],"Citation":[368],"Format:":[369],"Sophia":[370],"J.":[371,374],"Zhao,":[372],"Katelyn":[373],"Noronha,":[375],"Prateek":[376],"Bhardwaj,":[377],"Karlie":[378],"N.":[379],"Lucas,":[380],"Ranjini":[381],"K.":[382],"Sundaram,":[383],"Collin":[384],"D.":[385],"Heer,":[386],"Raffaella":[387],"Morotti,":[388],"Josh":[389],"Spurrier,":[390],"Mitch":[391],"Raponi,":[392],"Ranjit":[393],"S.":[394],"Bindra,":[395],"Juan":[396],"C.":[397],"Vasquez.":[398],"NAPRTsilencing":[399],"rhabdomyosarcoma":[401],"vulnerabilities":[404],"NAD+depletion":[406],"[abstract].":[407],"In:":[408],"Proceedings":[409],"American":[412],"Association":[413],"Research":[416],"Annual":[417],"Meeting":[418],"2024;":[419],"Part":[420],"1":[421],"(Regular":[422],"Abstracts);":[423],"2024":[424],"Apr":[425],"5-10;":[426],"San":[427],"Diego,":[428],"CA.":[429],"Philadelphia":[430],"(PA):":[431],"AACR;":[432],"Res":[434],"2024;84(6_Suppl):Abstract":[435],"nr":[436],"2866.":[437]},"counts_by_year":[],"updated_date":"2026-09-25T08:18:29.962427","created_date":"2024-03-23T00:00:00"}