{"id":"https://openalex.org/W4214869387","doi":"https://doi.org/10.3389/fonc.2021.723966","title":"Axitinib and HDAC Inhibitors Interact to Kill Sarcoma Cells","display_name":"Axitinib and HDAC Inhibitors Interact to Kill Sarcoma Cells","publication_year":2021,"publication_date":"2021-09-16","ids":{"openalex":"https://openalex.org/W4214869387","doi":"https://doi.org/10.3389/fonc.2021.723966"},"language":"en","primary_location":{"id":"doi:10.3389/fonc.2021.723966","doi":"https://doi.org/10.3389/fonc.2021.723966","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fonc.2021.723966","pdf_url":"https://www.frontiersin.org/articles/10.3389/fonc.2021.723966/pdf","source":{"id":"https://openalex.org/S2596394214","display_name":"Frontiers in Oncology","issn_l":"2234-943X","issn":["2234-943X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Oncology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/articles/10.3389/fonc.2021.723966/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5110573122","display_name":"Jane L. Roberts","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I184840846","display_name":"Virginia Commonwealth University","ror":"https://ror.org/02nkdxk79","country_code":"US","type":"education","lineage":["https://openalex.org/I184840846"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jane L. Roberts","raw_affiliation_strings":["Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States","Department of Pharmacology and Toxicology, Virginia Commonwealth University, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States","institution_ids":["https://openalex.org/I184840846"]},{"raw_affiliation_string":"Department of Pharmacology and Toxicology, Virginia Commonwealth University, United States","institution_ids":["https://openalex.org/I184840846"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113836377","display_name":"Laurence A. Booth","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I184840846","display_name":"Virginia Commonwealth University","ror":"https://ror.org/02nkdxk79","country_code":"US","type":"education","lineage":["https://openalex.org/I184840846"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Laurence Booth","raw_affiliation_strings":["Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, United States","Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, United States","institution_ids":["https://openalex.org/I184840846"]},{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, United States","institution_ids":["https://openalex.org/I184840846"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5080982053","display_name":"Andrew Stewart Poklepovic","orcid":"https://orcid.org/0000-0002-4015-5037","observed_orcids":["https://orcid.org/0000-0002-4015-5037"]},"institutions":[{"id":"https://openalex.org/I184840846","display_name":"Virginia Commonwealth University","ror":"https://ror.org/02nkdxk79","country_code":"US","type":"education","lineage":["https://openalex.org/I184840846"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Andrew Poklepovic","raw_affiliation_strings":["Department of Medicine, Virginia Commonwealth University, Richmond, VA, United States","Department of Medicine, Virginia Commonwealth University, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, Virginia Commonwealth University, Richmond, VA, United States","institution_ids":["https://openalex.org/I184840846"]},{"raw_affiliation_string":"Department of Medicine, Virginia Commonwealth University, United States","institution_ids":["https://openalex.org/I184840846"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5069980003","display_name":"Paul Dent","orcid":"https://orcid.org/0000-0001-6948-1875","observed_orcids":["https://orcid.org/0000-0001-6948-1875"]},"institutions":[{"id":"https://openalex.org/I184840846","display_name":"Virginia Commonwealth University","ror":"https://ror.org/02nkdxk79","country_code":"US","type":"education","lineage":["https://openalex.org/I184840846"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Paul Dent","raw_affiliation_strings":["Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, United States","Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, United States","institution_ids":["https://openalex.org/I184840846"]},{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, United States","institution_ids":["https://openalex.org/I184840846"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5069980003"],"corresponding_institution_ids":["https://openalex.org/I184840846"],"apc_list":{"value":2950,"currency":"USD","value_usd":2950},"apc_paid":{"value":2950,"currency":"USD","value_usd":2950},"fwci":0.314,"has_fulltext":true,"cited_by_count":4,"citation_normalized_percentile":{"value":0.49389942,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":93,"max":96},"biblio":{"volume":"11","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.9868000149726868,"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/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.9868000149726868,"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.005100000184029341,"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/T10587","display_name":"Autophagy in Disease and Therapy","score":0.002400000113993883,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"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/axitinib","display_name":"axitinib","score":0.9679999947547913},{"id":"https://openalex.org/keywords/histone-deacetylase-inhibitors","display_name":"histone deacetylase inhibitors","score":0.8650000095367432},{"id":"https://openalex.org/keywords/sarcoma","display_name":"sarcoma","score":0.9850000143051147},{"id":"https://openalex.org/keywords/drug-synergy","display_name":"drug synergy","score":0.6320000290870667},{"id":"https://openalex.org/keywords/akt-inhibition","display_name":"AKT inhibition","score":0.6010000109672546},{"id":"https://openalex.org/keywords/mtor-signaling","display_name":"mTOR signaling","score":0.8510000109672546},{"id":"https://openalex.org/keywords/raptor-phosphorylation","display_name":"Raptor phosphorylation","score":0.9480000138282776},{"id":"https://openalex.org/keywords/autophagy","display_name":"autophagy","score":0.7770000100135803},{"id":"https://openalex.org/keywords/ulk1","display_name":"ULK1","score":0.8759999871253967},{"id":"https://openalex.org/keywords/pd-l1","display_name":"PD-L1","score":0.8659999966621399},{"id":"https://openalex.org/keywords/entinostat","display_name":"entinostat","score":0.9490000009536743},{"id":"https://openalex.org/keywords/beclin-1","display_name":"Beclin-1","score":0.7350000143051147},{"id":"https://openalex.org/keywords/atg5","display_name":"ATG5","score":0.7329999804496765},{"id":"https://openalex.org/keywords/multikinase-inhibitor","display_name":"multikinase inhibitor","score":0.8100000023841858}],"concepts":[{"id":"https://openalex.org/C2776539811","wikidata":"https://www.wikidata.org/wiki/Q4830631","display_name":"Axitinib","level":4,"score":0.8575180768966675},{"id":"https://openalex.org/C2780124434","wikidata":"https://www.wikidata.org/wiki/Q12357464","display_name":"AMPK","level":4,"score":0.7569252848625183},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6573300957679749},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.6212913990020752},{"id":"https://openalex.org/C98490376","wikidata":"https://www.wikidata.org/wiki/Q14876060","display_name":"mTORC1","level":4,"score":0.5417407751083374},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.5305954217910767},{"id":"https://openalex.org/C203522944","wikidata":"https://www.wikidata.org/wiki/Q288322","display_name":"Autophagy","level":3,"score":0.5289889574050903},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.49965906143188477},{"id":"https://openalex.org/C71680706","wikidata":"https://www.wikidata.org/wiki/Q18032908","display_name":"ULK1","level":5,"score":0.48451322317123413},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.43654510378837585},{"id":"https://openalex.org/C2778208673","wikidata":"https://www.wikidata.org/wiki/Q894611","display_name":"Bosutinib","level":5,"score":0.43507134914398193},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.41867324709892273},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.3826959729194641},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3683389127254486},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.33668920397758484},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.30876046419143677},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.24229088425636292},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.1704428493976593},{"id":"https://openalex.org/C2779536868","wikidata":"https://www.wikidata.org/wiki/Q419940","display_name":"Dasatinib","level":4,"score":0.166584312915802},{"id":"https://openalex.org/C2777583451","wikidata":"https://www.wikidata.org/wiki/Q177094","display_name":"Imatinib","level":3,"score":0.06770217418670654},{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.0},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.0},{"id":"https://openalex.org/C2778695046","wikidata":"https://www.wikidata.org/wiki/Q421136","display_name":"Sorafenib","level":3,"score":0.0},{"id":"https://openalex.org/C2778019345","wikidata":"https://www.wikidata.org/wiki/Q1148337","display_name":"Hepatocellular carcinoma","level":2,"score":0.0}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.3389/fonc.2021.723966","doi":"https://doi.org/10.3389/fonc.2021.723966","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fonc.2021.723966","pdf_url":"https://www.frontiersin.org/articles/10.3389/fonc.2021.723966/pdf","source":{"id":"https://openalex.org/S2596394214","display_name":"Frontiers in Oncology","issn_l":"2234-943X","issn":["2234-943X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Oncology","raw_type":"journal-article"},{"id":"pmh:oai:europepmc.org:7376866","doi":null,"is_oa":true,"landing_page_url":"http://europepmc.org/pmc/articles/PMC8483767","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:5ff1f49d5e3c41198e86b3f06d7ce526","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/5ff1f49d5e3c41198e86b3f06d7ce526","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Oncology, Vol 11 (2021)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fonc.2021.723966","doi":"https://doi.org/10.3389/fonc.2021.723966","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fonc.2021.723966","pdf_url":"https://www.frontiersin.org/articles/10.3389/fonc.2021.723966/pdf","source":{"id":"https://openalex.org/S2596394214","display_name":"Frontiers in Oncology","issn_l":"2234-943X","issn":["2234-943X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Oncology","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9537000060081482,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320314504","display_name":"Commonwealth Health Research Board","ror":"https://ror.org/01x5qb890"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4214869387.pdf","grobid_xml":"https://content.openalex.org/works/W4214869387.grobid-xml"},"referenced_works_count":16,"referenced_works":["https://openalex.org/W1994767036","https://openalex.org/W2346042270","https://openalex.org/W2419599852","https://openalex.org/W2582602626","https://openalex.org/W2589656556","https://openalex.org/W2891563533","https://openalex.org/W2902295054","https://openalex.org/W2944423827","https://openalex.org/W2959407335","https://openalex.org/W2967881599","https://openalex.org/W2993949309","https://openalex.org/W2998819969","https://openalex.org/W2999104939","https://openalex.org/W3010005592","https://openalex.org/W3034136661","https://openalex.org/W3137878651"],"related_works":["https://openalex.org/W1994767036","https://openalex.org/W2959407335","https://openalex.org/W2753735822","https://openalex.org/W1940951496","https://openalex.org/W2017608962","https://openalex.org/W2475420094","https://openalex.org/W2746334444","https://openalex.org/W2019101589","https://openalex.org/W2014230291","https://openalex.org/W3215754378"],"abstract_inverted_index":{"We":[0],"have":[1],"extended":[2],"our":[3,205],"analyses":[4],"of":[5,52,75,79,96,105,110,122,141,155,168,175,185,210],"HDAC":[6,18,26,116,150,164,195,213],"inhibitor":[7,13,117,196],"biology":[8],"in":[9,29,149],"sarcoma.":[10],"The":[11],"multi-kinase":[12],"axitinib":[14,113,192,211],"interacted":[15,28,198],"with":[16,69,163],"multiple":[17],"inhibitors":[19,27,165,214],"to":[20,35,42,112,199],"kill":[21],"sarcoma":[22,220],"cells.":[23],"Axitinib":[24,161],"and":[25,39,41,59,62,78,93,114,128,137,172,188,193,212],"a":[30,88,156,218],"greater":[31],"than":[32],"additive":[33],"fashion":[34],"inactivate":[36],"AKT,":[37],"mTORC1":[38,92],"mTORC2,":[40],"increase":[43],"Raptor":[44,80],"S722/S792":[45,81],"phosphorylation.":[46],"Individually,":[47],"all":[48],"drugs":[49],"increased":[50],"phosphorylation":[51,74],"ATM":[53,98],"S1981,":[54],"AMPK\u03b1":[55,100],"T172,":[56],"ULK1":[57,64,76,85],"S317":[58,77],"ATG13":[60],"S318":[61],"reduced":[63,101,119,173],"S757":[65,86],"phosphorylation;":[66],"this":[67,106],"correlated":[68],"enhanced":[70,166],"autophagic":[71],"flux.":[72],"Increased":[73],"required":[82],"ATM-AMPK":[83],"signaling.":[84],"is":[87],"recognized":[89],"site":[90],"for":[91,134],"knock":[94,181],"down":[95,140,182],"either":[97],"or":[99,144],"the":[102,120,147,194,208],"drug-induced":[103],"dephosphorylation":[104],"site.":[107],"Combined":[108],"exposure":[109],"cells":[111],"an":[115],"significantly":[118,200],"expression":[121,154,167,174],"HDAC1,":[123],"HDAC2,":[124],"HDAC3,":[125],"HDAC4,":[126],"HDAC6":[127],"HDAC7.":[129],"No":[130],"response":[131],"was":[132,178],"observed":[133],"HDACs":[135,186],"10":[136],"11.":[138],"Knock":[139],"ULK1,":[142],"Beclin1":[143],"ATG5":[145],"prevented":[146],"decline":[148],"expression,":[151],"as":[152,217],"did":[153],"constitutively":[157],"active":[158],"mTOR":[159],"protein.":[160],"combined":[162],"Class":[169],"I":[170],"MHCA":[171],"PD-L1":[176],"which":[177],"recapitulated":[179],"via":[180],"studies,":[183],"particularly":[184],"1":[187],"3.":[189],"In":[190],"vivo,":[191],"entinostat":[197],"reduce":[201],"tumor":[202],"growth.":[203],"Collectively":[204],"findings":[206],"support":[207],"exploration":[209],"being":[215],"developed":[216],"novel":[219],"therapy.":[221]},"counts_by_year":[{"year":2024,"cited_by_count":2},{"year":2022,"cited_by_count":2}],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2022-03-05T00:00:00"}