{"id":"https://openalex.org/W4393989685","doi":"https://doi.org/10.1158/1538-7445.am2024-lb052","title":"Abstract LB052: PTP1B inhibitors activate a novel hypoxia-induced inflammatory cell death pathway in breast cancer","display_name":"Abstract LB052: PTP1B inhibitors activate a novel hypoxia-induced inflammatory cell death pathway in breast cancer","publication_year":2024,"publication_date":"2024-04-05","ids":{"openalex":"https://openalex.org/W4393989685","doi":"https://doi.org/10.1158/1538-7445.am2024-lb052"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2024-lb052","doi":"https://doi.org/10.1158/1538-7445.am2024-lb052","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2024-lb052","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/A5061899406","display_name":"Benjamin G. Neel","orcid":"https://orcid.org/0000-0002-9589-585X","observed_orcids":["https://orcid.org/0000-0002-9589-585X"]},"institutions":[{"id":"https://openalex.org/I4210086933","display_name":"NYU Langone Health","ror":"https://ror.org/005dvqh91","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210086933"]},{"id":"https://openalex.org/I4390039310","display_name":"NYU Langone\u2019s Laura and Isaac Perlmutter Cancer Center","ror":"https://ror.org/00sa8g751","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210086933","https://openalex.org/I4390039310"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Benjamin G. Neel","raw_affiliation_strings":["1NYU Langone Health Perlmutter Cancer Ctr., New York, NY;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1NYU Langone Health Perlmutter Cancer Ctr., New York, NY;","institution_ids":["https://openalex.org/I4210086933","https://openalex.org/I4390039310"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028460752","display_name":"Abhishek Bhardwaj","orcid":"https://orcid.org/0000-0003-4539-7497","observed_orcids":["https://orcid.org/0000-0003-4539-7497"]},"institutions":[{"id":"https://openalex.org/I4390039310","display_name":"NYU Langone\u2019s Laura and Isaac Perlmutter Cancer Center","ror":"https://ror.org/00sa8g751","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210086933","https://openalex.org/I4390039310"]},{"id":"https://openalex.org/I57206974","display_name":"New York University","ror":"https://ror.org/0190ak572","country_code":"US","type":"education","lineage":["https://openalex.org/I57206974"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Abhishek Bhardwaj","raw_affiliation_strings":["2Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY;","institution_ids":["https://openalex.org/I4390039310","https://openalex.org/I57206974"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Maria Antonelli","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4390039310","display_name":"NYU Langone\u2019s Laura and Isaac Perlmutter Cancer Center","ror":"https://ror.org/00sa8g751","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210086933","https://openalex.org/I4390039310"]},{"id":"https://openalex.org/I57206974","display_name":"New York University","ror":"https://ror.org/0190ak572","country_code":"US","type":"education","lineage":["https://openalex.org/I57206974"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Maria Antonelli","raw_affiliation_strings":["2Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY;","institution_ids":["https://openalex.org/I4390039310","https://openalex.org/I57206974"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5046586712","display_name":"Beatrix M. Ueberheide","orcid":"https://orcid.org/0000-0003-2512-0204","observed_orcids":["https://orcid.org/0000-0003-2512-0204"]},"institutions":[{"id":"https://openalex.org/I57206974","display_name":"New York University","ror":"https://ror.org/0190ak572","country_code":"US","type":"education","lineage":["https://openalex.org/I57206974"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Beatrix Ueberheide","raw_affiliation_strings":["33Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"33Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA, New York, NY","institution_ids":["https://openalex.org/I57206974"]}]}],"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":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"84","issue":"7_Supplement","first_page":"LB052","last_page":"LB052"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.8999000191688538,"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"}},"topics":[{"id":"https://openalex.org/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.8999000191688538,"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"}},{"id":"https://openalex.org/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.03959999978542328,"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"}},{"id":"https://openalex.org/T11591","display_name":"NF-\u03baB Signaling Pathways","score":0.010099999606609344,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/ptp1b-inhibitors","display_name":"PTP1B inhibitors","score":0.9570000171661377},{"id":"https://openalex.org/keywords/rnf213","display_name":"RNF213","score":0.8759999871253967},{"id":"https://openalex.org/keywords/cyld","display_name":"CYLD","score":0.5080000162124634},{"id":"https://openalex.org/keywords/hypoxia","display_name":"hypoxia","score":0.7450000047683716},{"id":"https://openalex.org/keywords/her2-positive-breast-cancer","display_name":"HER2-positive breast cancer","score":0.8920000195503235},{"id":"https://openalex.org/keywords/pyroptosis","display_name":"pyroptosis","score":0.9300000071525574},{"id":"https://openalex.org/keywords/nf-kappab-activation","display_name":"NF-\u03baB activation","score":0.8730000257492065},{"id":"https://openalex.org/keywords/endoplasmic-reticulum-stress","display_name":"endoplasmic reticulum stress","score":0.9079999923706055},{"id":"https://openalex.org/keywords/tumor-cell-death","display_name":"cancer cell death","score":0.7789999842643738},{"id":"https://openalex.org/keywords/ptp1b","display_name":"PTP1B","score":0.5649999976158142}],"concepts":[{"id":"https://openalex.org/C7836513","wikidata":"https://www.wikidata.org/wiki/Q1641506","display_name":"Hypoxia (environmental)","level":3,"score":0.7146134376525879},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.669285237789154},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.631673276424408},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.5491287708282471},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5242446064949036},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.42543458938598633},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.41692113876342773},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3640594482421875},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.35289859771728516},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2677382230758667},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.21837785840034485},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.18326324224472046},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.11738929152488708},{"id":"https://openalex.org/C540031477","wikidata":"https://www.wikidata.org/wiki/Q629","display_name":"Oxygen","level":2,"score":0.0},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2024-lb052","doi":"https://doi.org/10.1158/1538-7445.am2024-lb052","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2024-lb052","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","score":1.0,"display_name":"Good health and well-being"}],"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/W4385633249","https://openalex.org/W4404105387","https://openalex.org/W2175306372","https://openalex.org/W2470758117","https://openalex.org/W2326796800","https://openalex.org/W2081992478","https://openalex.org/W2260974271","https://openalex.org/W2275993376","https://openalex.org/W4321371618","https://openalex.org/W3162282698"],"abstract_inverted_index":{"Abstract":[0],"Dual":[1],"PTP1B/TC-PTP":[2],"(PTPN1/2)":[3],"inhibitors":[4,223],"are":[5],"in":[6,50,73,185,232],"clinical":[7,206],"trials":[8],"for":[9,180,242],"multiple":[10],"cancer":[11,24,28,47,234],"types,":[12],"primarily":[13],"because":[14],"they":[15,20],"augment":[16],"anti-tumor":[17],"immunity,":[18],"but":[19],"can":[21,35],"also":[22,70],"have":[23],"cell-autonomous":[25],"effects.":[26],"Hypoxic":[27],"cells":[29],"resist":[30],"many":[31],"anti-neoplastic":[32],"therapies":[33],"and":[34,61,67,78,86,99,108,152,253],"seed":[36],"recurrence.":[37],"We":[38,81],"found":[39],"previously":[40],"that":[41,69,84,133,161,188],"PTP1B":[42,85,150,209,222],"deficiency/inhibition":[43],"promotes":[44,96],"HER2+":[45,143],"breast":[46,233],"cell":[48,168,183,229],"death":[49,184,230],"hypoxia":[51],"by":[52],"activating":[53],"RNF213,":[54],"an":[55],"~600kDa":[56],"protein":[57],"containing":[58],"AAA-ATPase":[59],"domains":[60,65],"two":[62],"ubiquitin":[63],"ligase":[64],"(RING":[66],"RZ)":[68],"is":[71],"implicated":[72],"Moyamoya":[74],"disease":[75],"(MMD),":[76],"lipotoxicity,":[77],"innate":[79],"immunity.":[80],"now":[82],"report":[83],"ABL1/2":[87],"reciprocally":[88],"control":[89],"RNF213":[90,97,154,158],"phosphorylation":[91,95],"on":[92],"tyrosine-1275.":[93],"This":[94],"oligomerization":[98],"RZ":[100,104,140,163],"domain":[101,105,136,164],"activation.":[102],"The":[103],"ubiquitylates":[106],"CYLD/SPATA2,":[107],"together":[109,123],"with":[110,124,157],"the":[111,134,139,147,162,204,239],"LUBAC":[112],"complex,":[113],"induces":[114],"their":[115],"degradation.":[116],"Decreased":[117],"CYLD/SPATA2":[118],"causes":[119],"NF-\u03baB":[120],"activation,":[121],"which":[122],"hypoxia-induced":[125,227],"ER-stress":[126],"triggers":[127],"GDSMD-dependent":[128],"pyroptosis.":[129],"Mutagenesis":[130],"experiments":[131],"show":[132],"RING":[135],"negatively":[137],"regulates":[138],"domain.":[141],"CYLD-deleted":[142],"cell-derived":[144],"xenografts":[145],"phencopy":[146],"effects":[148],"of":[149,208,238],"deficiency,":[151],"reconstituting":[153],"knockout":[155],"lines":[156],"mutants":[159],"shows":[160],"mediates":[165],"PTP1B-dependent":[166],"tumor":[167,195],"death.":[169],"Our":[170],"results":[171],"identify":[172],"a":[173,225],"novel,":[174],"potentially":[175,197],"targetable":[176],"PTP1B/RNF213/CYCLD/SPATA":[177],"pathway":[178,231],"critical":[179],"controlling":[181],"inflammatory":[182,228],"hypoxic":[186,194],"tumors":[187,200],"could":[189],"be":[190],"exploited":[191],"to":[192],"target":[193],"cells,":[196],"turning":[198],"\u201ccold\u201d":[199],"\u201chot\u201d,":[201],"thereby":[202],"increasing":[203],"potential":[205],"utility":[207],"inhibitors.":[210],"Citation":[211],"Format:":[212],"Benjamin":[213],"G.":[214],"Neel,":[215],"Abhishek":[216],"Bhardwaj,":[217],"Maria":[218],"Antonelli,":[219],"Beatrix":[220],"Ueberheide.":[221],"activate":[224],"novel":[226],"[abstract].":[235],"In:":[236],"Proceedings":[237],"American":[240],"Association":[241],"Cancer":[243,265],"Research":[244],"Annual":[245],"Meeting":[246],"2024;":[247],"Part":[248],"2":[249],"(Late-Breaking,":[250],"Clinical":[251],"Trial,":[252],"Invited":[254],"Abstracts);":[255],"2024":[256],"Apr":[257],"5-10;":[258],"San":[259],"Diego,":[260],"CA.":[261],"Philadelphia":[262],"(PA):":[263],"AACR;":[264],"Res":[266],"2024;84(7_Suppl):Abstract":[267],"nr":[268],"LB052.":[269]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2024-04-06T00:00:00"}