{"id":"https://openalex.org/W4393072893","doi":"https://doi.org/10.1158/1538-7445.am2024-5147","title":"Abstract 5147: Identification of pharmacodynamic biomarkers in PBMCs and cancer cells for SIK2 kinase inhibitor therapy","display_name":"Abstract 5147: Identification of pharmacodynamic biomarkers in PBMCs and cancer cells for SIK2 kinase inhibitor therapy","publication_year":2024,"publication_date":"2024-03-22","ids":{"openalex":"https://openalex.org/W4393072893","doi":"https://doi.org/10.1158/1538-7445.am2024-5147"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2024-5147","doi":"https://doi.org/10.1158/1538-7445.am2024-5147","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.am2024-5147","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/A5101515086","display_name":"Hailing Yang","orcid":"https://orcid.org/0000-0001-6491-5945","observed_orcids":["https://orcid.org/0000-0001-6491-5945"]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hailing Yang","raw_affiliation_strings":["1UT MD Anderson Cancer Center, Houston, TX;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Center, Houston, TX;","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111381332","display_name":"Weiqun Mao","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Weiqun Mao","raw_affiliation_strings":["1UT MD Anderson Cancer Center, Houston, TX;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Center, Houston, TX;","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075890849","display_name":"Philip J. Rask","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Philip Rask","raw_affiliation_strings":["1UT MD Anderson Cancer Center, Houston, TX;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Center, Houston, TX;","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Markus Peter","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Markus Peter","raw_affiliation_strings":["2Greenfire Bio, Frisco, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Greenfire Bio, Frisco, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070879199","display_name":"Gayathri Swaminath","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gayathri Swaminath","raw_affiliation_strings":["2Greenfire Bio, Frisco, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Greenfire Bio, Frisco, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111898332","display_name":"Stephan Wade Morris","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Stephan W. Morris","raw_affiliation_strings":["2Greenfire Bio, Frisco, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Greenfire Bio, Frisco, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088086867","display_name":"Zhen L\u00fc","orcid":"https://orcid.org/0000-0002-9596-0148","observed_orcids":["https://orcid.org/0000-0002-9596-0148"]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Zhen Lu","raw_affiliation_strings":["1UT MD Anderson Cancer Center, Houston, TX;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Center, Houston, TX;","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5067595997","display_name":"Robert C. Bast","orcid":"https://orcid.org/0000-0003-4621-8462","observed_orcids":["https://orcid.org/0000-0003-4621-8462"]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Robert C. Bast","raw_affiliation_strings":["1UT MD Anderson Cancer Center, Houston, TX;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UT MD Anderson Cancer Center, Houston, TX;","institution_ids":["https://openalex.org/I1343551460"]}]}],"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":"5147","last_page":"5147"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.5116999745368958,"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.5116999745368958,"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/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.2727000117301941,"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/T10550","display_name":"Ovarian cancer diagnosis and treatment","score":0.10790000110864639,"subfield":{"id":"https://openalex.org/subfields/2743","display_name":"Reproductive Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/pharmacodynamic-markers","display_name":"pharmacodynamic biomarkers","score":0.9340000152587891},{"id":"https://openalex.org/keywords/peripheral-blood-mononuclear-cells","display_name":"peripheral blood mononuclear cells","score":0.9620000123977661},{"id":"https://openalex.org/keywords/ovarian-cancer","display_name":"ovarian cancer","score":0.7630000114440918},{"id":"https://openalex.org/keywords/breast-cancer","display_name":"breast cancer","score":1.0},{"id":"https://openalex.org/keywords/selenoprotein-p","display_name":"selenoprotein P","score":0.8339999914169312},{"id":"https://openalex.org/keywords/rnase1","display_name":"RNASE1","score":0.9900000095367432},{"id":"https://openalex.org/keywords/ms4a6a","display_name":"MS4A6A","score":0.9980000257492065},{"id":"https://openalex.org/keywords/ddit4","display_name":"DDIT4","score":0.9309999942779541},{"id":"https://openalex.org/keywords/nupr1","display_name":"NUPR1","score":0.9980000257492065},{"id":"https://openalex.org/keywords/interleukin-6","display_name":"interleukin-6","score":0.9769999980926514}],"concepts":[{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.7094323635101318},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.602790892124176},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5457661747932434},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.5009458065032959},{"id":"https://openalex.org/C137061746","wikidata":"https://www.wikidata.org/wiki/Q736033","display_name":"Peripheral blood mononuclear cell","level":3,"score":0.4976826012134552},{"id":"https://openalex.org/C116834253","wikidata":"https://www.wikidata.org/wiki/Q2039217","display_name":"Identification (biology)","level":2,"score":0.4729097783565521},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.40343213081359863},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.36961013078689575},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3524168133735657},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.27209407091140747},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.26873448491096497},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.24754664301872253},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.12135875225067139},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.0704321563243866},{"id":"https://openalex.org/C59822182","wikidata":"https://www.wikidata.org/wiki/Q441","display_name":"Botany","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2024-5147","doi":"https://doi.org/10.1158/1538-7445.am2024-5147","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.am2024-5147","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":0.98580002784729,"id":"https://metadata.un.org/sdg/3","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/W2903248705","https://openalex.org/W4281686000","https://openalex.org/W1794789812","https://openalex.org/W2495404144","https://openalex.org/W3185917834","https://openalex.org/W2914105091","https://openalex.org/W2009785633","https://openalex.org/W4252589640","https://openalex.org/W4293160875","https://openalex.org/W3133182048"],"abstract_inverted_index":{"Abstract":[0],"Salt-inducible":[1],"kinase":[2,9,45,388],"2":[3],"(SIK2)":[4],"is":[5,27,283],"an":[6,240],"AMPK":[7],"family":[8],"involved":[10],"in":[11,30,89,93,105,124,136,143,157,180,184,198,214,235,287,308,313,323,328,351,381],"multiple":[12],"signaling":[13,123],"pathways":[14],"including":[15],"the":[16,114,343,352,395],"LBK1-SIK-HDAC,":[17],"LKB1-SIK-CRTC/CREB,":[18],"PI3K-PKA-mTOR":[19],"and":[20,34,37,51,69,76,92,139,159,170,206,252,270,280,303,326,348,383],"Hippo":[21],"pathways.":[22],"The":[23,321],"expression":[24,273],"of":[25,32,43,49,58,67,80,116,274,291,317,345,354,378,394],"SIK2":[26,44,62,81,122,134,175,346,387],"significantly":[28],"upregulated":[29,284],"fraction":[31],"ovarian":[33,50,68,125,158,251],"breast":[35,52,70,160,254],"cancers,":[36],"associated":[38],"with":[39],"poor":[40],"prognosis.":[41],"Inhibition":[42],"activity":[46],"suppresses":[47],"growth":[48],"cancers":[53,85],"as":[54,56,335],"well":[55],"progression":[57],"acute":[59],"myeloid":[60],"leukemia.":[61],"inhibitors":[63,82,347],"synergistically":[64],"enhance":[65],"sensitivity":[66],"cancer":[71,126,137,161,236,255,384],"cells":[72,147,162,385],"to":[73,83,310,341],"paclitaxel,":[74],"carboplatin":[75],"PARP":[77],"inhibitors.":[78],"Utilization":[79],"treat":[84],"has":[86],"been":[87],"investigated":[88],"preclinical":[90],"studies":[91],"a":[94,118,185],"Phase":[95],"I":[96],"clinical":[97,106,339],"trial":[98],"(NCT04711161).":[99],"To":[100],"enable":[101],"pharmacodynamic":[102,379],"(PD)":[103],"analysis":[104,202],"studies,":[107],"we":[108,331],"have":[109],"developed":[110],"biomarkers":[111,337,380],"that":[112,151,173],"measure":[113],"effect":[115],"GRN-300,":[117],"SIK2/3":[119],"inhibitor,":[120],"on":[121],"cells.":[127,237],"Class":[128],"IIa":[129],"histone":[130],"deacetylases":[131],"(HDAC4/5/7)":[132],"are":[133,140,210,306],"substrates":[135],"cells;":[138],"also":[141,177,193],"expressed":[142,226],"peripheral":[144],"blood":[145],"mononuclear":[146],"(PBMCs).":[148],"We":[149,192,238],"found":[150],"GRN-300":[152,213,286,311],"decreased":[153],"phosphorylated":[154],"HDAC4/5/7":[155,324],"levels":[156,230],"(Lu":[163],"et":[164],"al.":[165],"J":[166],"Clin":[167],"Invest,":[168],"2022)":[169],"now":[171],"report":[172],"this":[174],"inhibitor":[176,389],"decreases":[178],"pHDAC4/5/7":[179],"PBMCs":[181,199,215,382],"ex":[182],"vivo":[183],"dose-dependent":[186],"manner":[187],"using":[188,245],"Western":[189],"blot":[190],"analysis.":[191],"identified":[194,239],"three":[195,275],"mRNA":[196,222,242,272,329],"markers":[197,223,330],"by":[200,212,248,285],"RNAseq":[201,246],"-":[203,208,277,282,298,305],"SEPP1,":[204],"RNASE1":[205],"MS4A6A":[207],"which":[209],"up-regulated":[211],"isolated":[216],"from":[217],"healthy":[218],"donors.":[219],"However,":[220],"these":[221],"were":[224],"either":[225],"at":[227],"very":[228],"low":[229],"or":[231],"not":[232],"dramatically":[233],"changed":[234],"additional":[241],"marker":[243],"panel":[244],"technology":[247],"screening":[249],"seven":[250],"six":[253],"cell":[256,293,319],"lines:":[257],"A2780,":[258],"Caov3,":[259],"IGROV1,":[260],"OC316,":[261],"OVCAR3,":[262],"OVCAR8,":[263],"SKOv3ip,":[264],"BT549,":[265],"Cal51,":[266],"HCC1937,":[267],"MDA-MB-231,":[268],"MDA-MB-436":[269],"MDA-MB-468.":[271],"genes":[276,297],"DDIT4,":[278],"NUPR1":[279],"IL6":[281],"more":[288,314],"than":[289,315],"9":[290],"13":[292,318],"lines":[294],"tested.":[295],"Five":[296],"ID1,":[299],"ID2,":[300],"ID3,":[301],"ID4":[302],"TGFBI":[304],"down-regulated":[307],"response":[309],"treatment":[312],"10":[316],"lines.":[320],"decrease":[322],"phosphorylation,":[325],"alterations":[327],"discovered":[332],"could":[333],"serve":[334],"PD":[336],"for":[338,386,398],"trials":[340],"evaluate":[342],"effects":[344],"provide":[349],"insights":[350],"mechanisms":[353],"drug":[355],"action.":[356],"Citation":[357],"Format:":[358],"Hailing":[359],"Yang,":[360],"Weiqun":[361],"Mao,":[362],"Philip":[363],"Rask,":[364],"Markus":[365],"Peter,":[366],"Gayathri":[367],"Swaminath,":[368],"Stephan":[369],"W.":[370],"Morris,":[371],"Zhen":[372],"Lu,":[373],"Robert":[374],"C.":[375],"Bast.":[376],"Identification":[377],"therapy":[390],"[abstract].":[391],"In:":[392],"Proceedings":[393],"American":[396],"Association":[397],"Cancer":[399,417],"Research":[400],"Annual":[401],"Meeting":[402],"2024;":[403],"Part":[404],"1":[405],"(Regular":[406],"Abstracts);":[407],"2024":[408],"Apr":[409],"5-10;":[410],"San":[411],"Diego,":[412],"CA.":[413],"Philadelphia":[414],"(PA):":[415],"AACR;":[416],"Res":[418],"2024;84(6_Suppl):Abstract":[419],"nr":[420],"5147.":[421]},"counts_by_year":[],"updated_date":"2026-09-27T08:07:27.782135","created_date":"2024-03-23T00:00:00"}