{"id":"https://openalex.org/W4322769764","doi":"https://doi.org/10.1158/1538-7445.sabcs22-p6-10-10","title":"Abstract P6-10-10: Genetic alterations in breast cancer associated with MDM2 dependency and sensitivity to the MDM2 inhibitor milademetan","display_name":"Abstract P6-10-10: Genetic alterations in breast cancer associated with MDM2 dependency and sensitivity to the MDM2 inhibitor milademetan","publication_year":2023,"publication_date":"2023-03-01","ids":{"openalex":"https://openalex.org/W4322769764","doi":"https://doi.org/10.1158/1538-7445.sabcs22-p6-10-10"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.sabcs22-p6-10-10","doi":"https://doi.org/10.1158/1538-7445.sabcs22-p6-10-10","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-10-10","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/A5005286764","display_name":"Fran\u00e7ois\u2010Cl\u00e9ment Bidard","orcid":"https://orcid.org/0000-0001-5932-8949","observed_orcids":["https://orcid.org/0000-0001-5932-8949"]},"institutions":[{"id":"https://openalex.org/I80043","display_name":"Institut Curie","ror":"https://ror.org/04t0gwh46","country_code":"FR","type":"nonprofit","lineage":["https://openalex.org/I80043"]}],"countries":["FR"],"is_corresponding":false,"raw_author_name":"Francois-Clement Bidard","raw_affiliation_strings":["1Institut Curie, Paris, France"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Institut Curie, Paris, France","institution_ids":["https://openalex.org/I80043"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079081967","display_name":"Diana Bello Roufai","orcid":"https://orcid.org/0000-0002-2817-7866","observed_orcids":["https://orcid.org/0000-0002-2817-7866"]},"institutions":[{"id":"https://openalex.org/I80043","display_name":"Institut Curie","ror":"https://ror.org/04t0gwh46","country_code":"FR","type":"nonprofit","lineage":["https://openalex.org/I80043"]}],"countries":["FR"],"is_corresponding":false,"raw_author_name":"Diana Bello Roufai","raw_affiliation_strings":["2Institut Curie, France"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Institut Curie, France","institution_ids":["https://openalex.org/I80043"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006734008","display_name":"Arielle J. Medford","orcid":"https://orcid.org/0000-0002-0829-183X","observed_orcids":["https://orcid.org/0000-0002-0829-183X"]},"institutions":[{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Arielle J. Medford","raw_affiliation_strings":["3Massachusetts General Hospital Cancer Center/Dana Farber Cancer Institute"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Massachusetts General Hospital Cancer Center/Dana Farber Cancer Institute","institution_ids":["https://openalex.org/I4210087915","https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037183800","display_name":"Vijaya G. Tirunagaru","orcid":"https://orcid.org/0000-0002-6505-8858","observed_orcids":["https://orcid.org/0000-0002-6505-8858"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Vijaya Tirunagaru","raw_affiliation_strings":["4Rain Therapeutics, Inc"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"4Rain Therapeutics, Inc","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034705456","display_name":"Robert Charles Doebele","orcid":"https://orcid.org/0000-0001-6728-6857","observed_orcids":["https://orcid.org/0000-0001-6728-6857"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Robert C. Doebele","raw_affiliation_strings":["5Rain Therapeutics, Inc"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"5Rain Therapeutics, Inc","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5034972183","display_name":"Aditya Bardia","orcid":"https://orcid.org/0000-0003-4885-1157","observed_orcids":["https://orcid.org/0000-0003-4885-1157"]},"institutions":[{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Aditya Bardia","raw_affiliation_strings":["6Massachusetts General Hospital Cancer Center, Boston, Massachusetts"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"6Massachusetts General Hospital Cancer Center, Boston, Massachusetts","institution_ids":["https://openalex.org/I4210087915"]}]}],"institutions":[],"countries_distinct_count":2,"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":"83","issue":"5_Supplement","first_page":"P6","last_page":"10"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10583","display_name":"Cancer-related Molecular Pathways","score":0.9976000189781189,"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/T10583","display_name":"Cancer-related Molecular Pathways","score":0.9976000189781189,"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/T10183","display_name":"Breast Cancer Treatment Studies","score":0.001500000013038516,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":9.999999747378752e-05,"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/mdm2","display_name":"MDM2","score":0.8550000190734863},{"id":"https://openalex.org/keywords/mdm2-inhibitors","display_name":"MDM2 inhibitors","score":0.6620000004768372},{"id":"https://openalex.org/keywords/milademetan","display_name":"milademetan","score":0.9959999918937683},{"id":"https://openalex.org/keywords/breast-cancer","display_name":"breast cancer","score":0.8429999947547913},{"id":"https://openalex.org/keywords/mdm2-amplification","display_name":"MDM2 amplification","score":0.9120000004768372},{"id":"https://openalex.org/keywords/cdkn2a-loss","display_name":"CDKN2A loss","score":0.8939999938011169},{"id":"https://openalex.org/keywords/p14arf","display_name":"p14ARF","score":0.906000018119812},{"id":"https://openalex.org/keywords/hormone-receptor-positive-breast-cancer","display_name":"hormone receptor-positive breast cancer","score":0.9620000123977661},{"id":"https://openalex.org/keywords/xenograft-models","display_name":"xenograft models","score":0.7089999914169312},{"id":"https://openalex.org/keywords/drug-sensitivity","display_name":"drug sensitivity","score":0.5059999823570251}],"concepts":[{"id":"https://openalex.org/C2780265364","wikidata":"https://www.wikidata.org/wiki/Q5009957","display_name":"CDKN2A","level":3,"score":0.8310773372650146},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.7091859579086304},{"id":"https://openalex.org/C2776192174","wikidata":"https://www.wikidata.org/wiki/Q18028978","display_name":"Mdm2","level":3,"score":0.6938300132751465},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.6613304018974304},{"id":"https://openalex.org/C2776750431","wikidata":"https://www.wikidata.org/wiki/Q7117832","display_name":"p14arf","level":5,"score":0.5787011384963989},{"id":"https://openalex.org/C29906990","wikidata":"https://www.wikidata.org/wiki/Q1440688","display_name":"Frameshift mutation","level":4,"score":0.5657891631126404},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5482646822929382},{"id":"https://openalex.org/C2781187634","wikidata":"https://www.wikidata.org/wiki/Q20969980","display_name":"KRAS","level":4,"score":0.4290277361869812},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.42418742179870605},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.36648720502853394},{"id":"https://openalex.org/C555283112","wikidata":"https://www.wikidata.org/wiki/Q1637543","display_name":"Carcinogenesis","level":3,"score":0.3379243314266205},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2747989296913147},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.20509183406829834},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.19936233758926392},{"id":"https://openalex.org/C2778264664","wikidata":"https://www.wikidata.org/wiki/Q422445","display_name":"Tumor suppressor gene","level":4,"score":0.1823747754096985},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.13281729817390442},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.11873966455459595},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.sabcs22-p6-10-10","doi":"https://doi.org/10.1158/1538-7445.sabcs22-p6-10-10","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-10-10","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":0.9763000011444092,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"score":0.8600000143051147,"display_name":"Good health and well-being","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/W4200549171","https://openalex.org/W4282914532","https://openalex.org/W4286295703","https://openalex.org/W4200383547","https://openalex.org/W4282965409","https://openalex.org/W2157666410","https://openalex.org/W4412026769","https://openalex.org/W4410844740","https://openalex.org/W4286297237","https://openalex.org/W4406847197"],"abstract_inverted_index":{"Abstract":[0],"Background:":[1],"Murine":[2],"double":[3],"minute":[4],"2":[5,460],"(MDM2),":[6],"a":[7,65,173,185,352,357],"potent":[8],"negative":[9],"regulator":[10,41],"of":[11,31,45,62,95,98,105,145,168,374,387,447,455,479,533],"p53,":[12],"promotes":[13],"tumorigenesis":[14],"if":[15],"dysregulated.":[16],"MDM2":[17,24,27,40,46,63,78,111,149,203,226,269,275,291,393,403,422,429,470,521,527],"dysregulation":[18],"occurs":[19],"via":[20],"different":[21],"mechanisms,":[22],"including":[23,75],"gene":[25],"amplification,":[26,404],"overexpression,":[28],"and":[29,47,83,92,102,155,162,192,229,331,372,405,414,437,442,469,474,523],"loss":[30,158,231,267,272],"cyclin-dependent":[32],"kinase":[33],"inhibitor":[34,112,430,528],"2A":[35],"(CDKN2A),":[36],"which":[37],"encodes":[38],"the":[39,58,90,109,143,220,254,411,428,444,526,534],"p14ARF.":[42],"Combined":[43],"inactivation":[44],"GATA3":[48,146,183,190,222,260,265,285,401],"in":[49,172,195,210,219,243,248,279,315,326,342,410,435,449,463,483,494,516],"hormone":[50],"receptor-positive":[51],"(HR+)":[52],"breast":[53,86,100,137,178,186,198,213,235,251,281,307,329,345,363,398,440,517],"cancer":[54,138,179,199,308,346,364,518],"is":[55,64,408],"lethal":[56],"to":[57,108,313,525],"cell.":[59],"Pharmacologic":[60],"inhibition":[61,394],"rational":[66],"therapeutic":[67],"strategy":[68],"for":[69],"MDM2-dependent,":[70],"TP53":[71,135,175,211,249,295,396,467],"wildtype":[72],"(WT)":[73],"tumors,":[74,236],"tumors":[76,107,465,485],"with":[77,240,359,377,420,466,486,520],"amplification":[79,150,227],"or":[80,493],"CDKN2A":[81,156,230,288,406,487],"loss,":[82,289],"GATA3-mutant":[84,305,327,436],"HR+":[85,177,244,280,328,344,412,439],"cancers.":[87],"We":[88],"determined":[89,160],"frequency":[91,144,386],"associated":[93,419,519],"characteristics":[94],"genetic":[96,388,416],"alterations":[97,389,515],"MDM2-dependent":[99],"cancers,":[101,441],"evaluated":[103,171],"sensitivity":[104,524],"these":[106,298,415,450],"small-molecule":[110],"milademetan":[113,169,314,378,431,448,456,480,529],"(RAIN-32).":[114],"Methods:":[115],"Genomic":[116],"data":[117,425],"were":[118,238,257],"obtained":[119],"from":[120,140],"three":[121],"datasets:":[122],"METABRIC;":[123],"TCGA":[124],"PanCancer":[125],"Atlas,":[126],"GDC":[127],"v23.0":[128],"(April":[129],"2020);":[130],"AACR":[131],"Genie,":[132],"v11.":[133],"Among":[134],"WT":[136,176,212,250,296,397,468],"samples":[139],"each":[141],"dataset,":[142],"frameshift":[147,223],"mutations,":[148,286,402],"(copy":[151],"number":[152],"[CN]":[153],"\u226512),":[154],"homozygous":[157],"was":[159,170,311],"individually":[161],"as":[163],"co-alterations.":[164],"The":[165,385],"antitumoral":[166],"activity":[167,325,341,434],"GATA3-mutant,":[174],"cell":[180,309],"line":[181,310],"(MCF7":[182,189],"G336fs*17),":[184],"xenograft":[187,330],"model":[188],"G335fs),":[191],"ex":[193],"vivo":[194],"MDM2-amplified":[196,343,362,438],"patient-derived":[197],"organoids":[200,347],"(CTG-2810,":[201],"ER+/PR+/HER2\u2013,":[202],"CN":[204,262,270,292,366,471],"8).":[205],"Results:":[206],"Genetic":[207,514],"alteration":[208],"frequencies":[209,242,247],"cancers":[214,252,282,399],"by":[215,392],"dataset":[216],"are":[217,418,490],"shown":[218],"Table.":[221,496],"mutations":[224],"(7.3\u201311.7%),":[225],"(0.3\u20131.1%),":[228],"(0.2\u20131.2%)":[232],"occurred":[233],"across":[234,253],"but":[237],"found":[239],"highest":[241],"tumors.":[245,451],"Co-alteration":[246],"aforementioned":[255],"datasets":[256],"<":[258],"1%:":[259],"mutations/MDM2":[261],"\u226512":[263],"(0.2\u20130.3%);":[264],"mutations/CDKN2A":[266],"(0.1\u20130.2%);":[268],"\u226512/CDKN2A":[271],"(0%).":[273],"Mean":[274],"expression":[276],"(log2":[277],"(TPM+1))":[278],"(TCGA)":[283],"were:":[284],"5.12;":[287],"5.88;":[290],"\u226512,":[293],"8.13,":[294],"without":[297],"alterations,":[299],"4.78;":[300],"mutant":[301],"TP53,":[302],"4.35.":[303],"A":[304],"ER+":[306],"sensitive":[312],"vitro":[316],"(IC50":[317,348],"126":[318],"nM).":[319],"Milademetan":[320,338],"100":[321],"mg/kg":[322],"displayed":[323,340],"antitumor":[324,433],"PDX":[332],"models":[333],"(p<":[334],"0.05":[335],"vs.":[336],"vehicle).":[337],"also":[339],"0.2":[349],"\u03bcM).":[350],"In":[351],"phase":[353],"I":[354],"study":[355,462,478],"(NCT01877382),":[356],"patient":[358],"heavily":[360],"pretreated":[361],"(MDM2":[365],"16.8)":[367],"had":[368],"tumor":[369],"shrinkage":[370],"(18.2%)":[371],"PFS":[373],"7.3":[375],"months":[376],"(orally":[379],"260":[380],"mg":[381],"3/14":[382],"days).":[383],"Conclusions:":[384],"potentially":[390],"targetable":[391],"among":[395],"(i.e.,":[400],"loss)":[407,488],"greatest":[409],"subset,":[413],"biomarkers":[417],"higher":[421],"expression.":[423],"Preclinical":[424],"show":[426],"that":[427],"has":[432],"support":[443],"clinical":[445,453],"evaluation":[446],"Two":[452],"trials":[454],"\u2013":[457,489],"MANTRA-2":[458],"(Phase":[459,476],"basket":[461],"solid":[464,484],"\u226512;":[472],"NCT05012397)":[473],"MANTRA-4":[475],"1":[477],"+":[481],"atezolizumab":[482],"enrolling":[491],"patients":[492],"planning.":[495],"Citation":[497],"Format:":[498],"Francois-Clement":[499],"Bidard,":[500],"Diana":[501],"Bello":[502],"Roufai,":[503],"Arielle":[504],"J.":[505],"Medford,":[506],"Vijaya":[507],"Tirunagaru,":[508],"Robert":[509],"C.":[510],"Doebele,":[511],"Aditya":[512],"Bardia.":[513],"dependency":[522],"[abstract].":[530],"In:":[531],"Proceedings":[532],"2022":[535,541],"San":[536,544],"Antonio":[537],"Breast":[538],"Cancer":[539,550],"Symposium;":[540],"Dec":[542],"6-10;":[543],"Antonio,":[545],"TX.":[546],"Philadelphia":[547],"(PA):":[548],"AACR;":[549],"Res":[551],"2023;83(5":[552],"Suppl):Abstract":[553],"nr":[554],"P6-10-10.":[555]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2023-03-03T00:00:00"}
