{"id":"https://openalex.org/W3083368554","doi":"https://doi.org/10.1158/1538-7445.am2020-2248","title":"Abstract 2248: Paclitaxel-induced micronucleation activates pro-inflammatory cGAS/STING signaling in triple negative breast cancer","display_name":"Abstract 2248: Paclitaxel-induced micronucleation activates pro-inflammatory cGAS/STING signaling in triple negative breast cancer","publication_year":2020,"publication_date":"2020-08-15","ids":{"openalex":"https://openalex.org/W3083368554","doi":"https://doi.org/10.1158/1538-7445.am2020-2248","mag":"3083368554"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2020-2248","doi":"https://doi.org/10.1158/1538-7445.am2020-2248","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2020-2248","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":["cwts-core","doyens","jufo-3","ki-jl-3","medline","norway-2"],"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/A5060805984","display_name":"Yang Hu","orcid":"https://orcid.org/0000-0002-3068-7136","observed_orcids":["https://orcid.org/0000-0002-3068-7136"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yang Hu","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054686355","display_name":"Ning Yi Jin","orcid":"https://orcid.org/0000-0002-6689-4671","observed_orcids":["https://orcid.org/0000-0002-6689-4671"]},"institutions":[{"id":"https://openalex.org/I52357470","display_name":"The Ohio State University","ror":"https://ror.org/00rs6vg23","country_code":"US","type":"education","lineage":["https://openalex.org/I52357470"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ning Jin","raw_affiliation_strings":["2Ohio State University, Columbus, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Ohio State University, Columbus, OH","institution_ids":["https://openalex.org/I52357470"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065697009","display_name":"Baraa K. Manasrah","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Baraa K. Manasrah","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090208590","display_name":"Stephanie M. McGregor","orcid":"https://orcid.org/0000-0002-7940-1143","observed_orcids":["https://orcid.org/0000-0002-7940-1143"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Stephanie M. McGregor","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071363739","display_name":"Christina M. Scribano","orcid":"https://orcid.org/0000-0002-4002-5101","observed_orcids":["https://orcid.org/0000-0002-4002-5101"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christina Scribano","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022088555","display_name":"John B. Tucker","orcid":"https://orcid.org/0000-0002-5009-934X","observed_orcids":["https://orcid.org/0000-0002-5009-934X"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John B. Tucker","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000551343","display_name":"Rachel Yan","orcid":"https://orcid.org/0000-0002-6718-142X","observed_orcids":["https://orcid.org/0000-0002-6718-142X"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rachel Yan","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086139307","display_name":"Robert F. Lera","orcid":"https://orcid.org/0000-0001-8713-4279","observed_orcids":["https://orcid.org/0000-0001-8713-4279"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Robert F. Lera","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008049256","display_name":"Beth A. A. Weaver","orcid":"https://orcid.org/0000-0002-7830-3816","observed_orcids":["https://orcid.org/0000-0002-7830-3816"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Beth A. Weaver","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5050180604","display_name":"Mark E. Burkard","orcid":"https://orcid.org/0000-0002-4215-7722","observed_orcids":["https://orcid.org/0000-0002-4215-7722"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mark E. Burkard","raw_affiliation_strings":["1University of Wisconsin-Madison, Madison, WI;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Wisconsin-Madison, Madison, WI;","institution_ids":["https://openalex.org/I135310074"]}]}],"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":"80","issue":"16_Supplement","first_page":"2248","last_page":"2248"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11668","display_name":"interferon and immune responses","score":0.7904999852180481,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11668","display_name":"interferon and immune responses","score":0.7904999852180481,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.13369999825954437,"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/T10580","display_name":"Immunotherapy and Immune Responses","score":0.022199999541044235,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/paclitaxel","display_name":"paclitaxel","score":0.9890000224113464},{"id":"https://openalex.org/keywords/micronucleation","display_name":"micronucleation","score":0.8080000281333923},{"id":"https://openalex.org/keywords/cgas-sting-pathway","display_name":"cGAS-STING pathway","score":0.906000018119812},{"id":"https://openalex.org/keywords/triple-negative-breast-cancer","display_name":"triple-negative breast cancer","score":0.9869999885559082},{"id":"https://openalex.org/keywords/immunogenic-chemotherapy","display_name":"immunogenic chemotherapy","score":0.6480000019073486},{"id":"https://openalex.org/keywords/interferon-beta","display_name":"interferon-beta","score":0.7200000286102295},{"id":"https://openalex.org/keywords/2-3-cgamp","display_name":"2'-3'-cGAMP","score":0.8360000252723694},{"id":"https://openalex.org/keywords/tumor-infiltrating-lymphocytes","display_name":"tumor-infiltrating lymphocytes","score":0.7820000052452087},{"id":"https://openalex.org/keywords/macrophage-polarization","display_name":"macrophage polarization","score":0.847000002861023},{"id":"https://openalex.org/keywords/neoadjuvant-chemotherapy","display_name":"neoadjuvant chemotherapy","score":0.6499999761581421},{"id":"https://openalex.org/keywords/mda-mb-231-cells","display_name":"MDA-MB-231 cells","score":0.7409999966621399},{"id":"https://openalex.org/keywords/thp-1-cells","display_name":"THP-1 cells","score":0.6579999923706055}],"concepts":[{"id":"https://openalex.org/C2777292972","wikidata":"https://www.wikidata.org/wiki/Q423762","display_name":"Paclitaxel","level":3,"score":0.9013161659240723},{"id":"https://openalex.org/C2777511904","wikidata":"https://www.wikidata.org/wiki/Q425227","display_name":"Taxane","level":4,"score":0.7069427967071533},{"id":"https://openalex.org/C45080847","wikidata":"https://www.wikidata.org/wiki/Q1658004","display_name":"Micronucleus test","level":3,"score":0.7054807543754578},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6028039455413818},{"id":"https://openalex.org/C2780110267","wikidata":"https://www.wikidata.org/wiki/Q7843332","display_name":"Triple-negative breast cancer","level":4,"score":0.555189847946167},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.45052534341812134},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.4190346896648407},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3872222900390625},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3639702796936035},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.24262458086013794},{"id":"https://openalex.org/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.1373128890991211}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2020-2248","doi":"https://doi.org/10.1158/1538-7445.am2020-2248","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2020-2248","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":["cwts-core","doyens","jufo-3","ki-jl-3","medline","norway-2"],"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":0.9922999739646912}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.8500000238418579}],"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/W2021885202","https://openalex.org/W2585639202","https://openalex.org/W4380048398","https://openalex.org/W1980013663","https://openalex.org/W2567870879","https://openalex.org/W4243246651","https://openalex.org/W2289487854","https://openalex.org/W2046196715","https://openalex.org/W2109641043","https://openalex.org/W2073970221"],"abstract_inverted_index":{"Abstract":[0],"Introduction:":[1],"Paclitaxel":[2,50],"(TaxolTM)":[3],"is":[4,25,48,210,256,272],"a":[5,327,331,355,363],"blockbuster":[6],"chemotherapy":[7],"used":[8],"for":[9,182,316,366,378,438],"solid":[10],"tumors":[11],"including":[12],"breast":[13,17,348,425],"cancer.":[14],"In":[15,248],"triple-negative":[16],"cancer":[18,349,368,426],"(TNBC),":[19],"nab-paclitaxel":[20,34],"plus":[21],"PD-L1":[22],"inhibitor,":[23],"atezolizumab,":[24],"now":[26],"approved":[27],"based":[28],"on":[29,55,98,108,124,147],"increased":[30,257],"survival":[31],"compared":[32],"with":[33,282,294,322,386],"alone.":[35],"We":[36,88,152,200],"hypothesize":[37],"that":[38,77,202],"there":[39],"may":[40,361,373],"be":[41],"an":[42,300,308],"interaction":[43],"by":[44,111,197],"which":[45,58,271],"taxane":[46],"therapy":[47],"immunogenic.":[49],"induces":[51],"aberrant":[52],"cell":[53,100,227,246,350,369],"division":[54],"multipolar":[56],"spindles,":[57],"often":[59,205],"results":[60],"in":[61,85,161,179,212,217,238,244,274,285,310,347,383,422],"formation":[62,183],"of":[63,68,92,96,122,145,149,170,184,195,223,252,261,279,318,337,430,434],"multiple":[64],"small":[65],"nuclei.":[66],"Some":[67],"these":[69,163],"resemble":[70],"micronuclei.":[71,207],"Here,":[72],"we":[73,118,135,166,306],"test":[74,167],"the":[75,90,120,143,168,192,225,344,375,379,431,435],"hypothesis":[76],"taxane-induced":[78],"micronuclei":[79,110,185,311,341],"activate":[80,343],"cGAS-STING":[81,345],"to":[82,141,157,234,302,330,342,353],"increase":[83,309],"immunogenicity":[84],"TNBC.":[86],"Methods:":[87],"evaluate":[89,119,142,158],"impact":[91,121,144],"clinically":[93],"relevant":[94],"doses":[95],"paclitaxel":[97,123,146,172,196,315,338],"TNBC":[99],"lines":[101,351],"MDA-MB-231,":[102],"MDA-MB-453,":[103],"MDA-MB-468,":[104],"BT-549":[105],"and":[106,116,127,131,138,186,254,265,312,352,445],"HCC-1806":[107],"generating":[109],"immunofluorescence":[112],"microscopy.":[113],"Using":[114],"immunoblotting":[115],"qPCR,":[117],"cGAS":[125,155,208,275],"recruitment":[126,209],"activation,":[128,130,270],"STING":[129,269],"interferon-beta":[132,357],"production.":[133],"Furthermore,":[134,305],"co-culture":[136],"MDA-MB-231":[137,249,283,291],"THP-1":[139,150,280,297],"cells":[140,204,284,292,298],"polarization":[148],"macrophages.":[151],"employ":[153],"CRISPR-mediated":[154],"knockout":[156,276],"its":[159],"role":[160],"mediating":[162],"effects.":[164],"Finally,":[165],"effect":[169],"neoadjuvant":[171],"(80":[173],"mg/m2":[174],"qw,":[175],"16":[176],"treatments/4":[177],"cycles)":[178],"4":[180,319],"patients":[181],"tumor-infiltrating":[187],"lymphocytes":[188],"20":[189],"hours":[190],"after":[191,258,314],"third":[193],"treatment":[194],"H&E.":[198],"Results:":[199],"observe":[201,307],"post-mitotic":[203,364],"contain":[206],"detected":[211],"some":[213],"micronuclei,":[214],"more":[215],"commonly":[216],"multinucleated":[218],"cells.":[219,277],"With":[220],"three":[221],"days":[222],"paclitaxel,":[224,286,295],"cGAS-positive":[226],"population":[228],"increases":[229],"from":[230,290,299,326],"9%":[231],"(+/-":[232,236],"1.3)":[233],"34%":[235],"2.4)":[237],"MDA-MB-231.":[239],"Similar":[240],"trends":[241],"are":[242],"observed":[243],"other":[245],"lines.":[247],"cells,":[250],"synthesis":[251],"2'3'-cGAMP":[253],"IFN-beta":[255],"paclitaxel.":[259],"Upregulation":[260],"interferon":[262],"stimulated":[263],"genes":[264],"phospho-proteins":[266],"also":[267],"supports":[268],"abolished":[273],"Co-culture":[278],"macrophages":[281],"or":[287],"conditioned":[288],"media":[289],"pre-treated":[293],"polarizes":[296],"M0":[301],"M1":[303],"phenotype.":[304],"TILs":[313],"3":[317],"patient":[320,324],"samples":[321],"one":[323],"converting":[325],"plasma":[328],"cell-rich":[329],"lymphocyte-rich":[332],"infiltrate.":[333],"Conclusions:":[334],"Physiologic":[335],"levels":[336],"can":[339],"generate":[340],"pathway":[346],"induce":[354],"pro-inflammatory":[356,419],"driven":[358],"response.":[359],"This":[360],"present":[362],"mechanism":[365],"paclitaxel-mediated":[367],"death.":[370],"These":[371],"data":[372],"provide":[374],"mechanistic":[376],"basis":[377],"high":[380],"efficacy":[381],"seen":[382],"combining":[384],"taxanes":[385],"immunotherapies.":[387],"Citation":[388],"Format:":[389],"Yang":[390],"Hu,":[391],"Ning":[392],"Jin,":[393],"Baraa":[394],"K.":[395],"Manasrah,":[396],"Stephanie":[397],"M.":[398],"McGregor,":[399],"Christina":[400],"Scribano,":[401],"John":[402],"B.":[403],"Tucker,":[404],"Rachel":[405],"Yan,":[406],"Robert":[407],"F.":[408],"Lera,":[409],"Beth":[410],"A.":[411],"Weaver,":[412],"Mark":[413],"E.":[414],"Burkard.":[415],"Paclitaxel-induced":[416],"micronucleation":[417],"activates":[418],"cGAS/STING":[420],"signaling":[421],"triple":[423],"negative":[424],"[abstract].":[427],"In:":[428],"Proceedings":[429],"Annual":[432],"Meeting":[433],"American":[436],"Association":[437],"Cancer":[439,451],"Research":[440],"2020;":[441],"2020":[442],"Apr":[443],"27-28":[444],"Jun":[446],"22-24.":[447],"Philadelphia":[448],"(PA):":[449],"AACR;":[450],"Res":[452],"2020;80(16":[453],"Suppl):Abstract":[454],"nr":[455],"2248.":[456]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2025-10-10T00:00:00"}