{"id":"https://openalex.org/W1566690127","doi":null,"title":"Downregulation of Noxa by RAF/MEK inhibition counteracts cell death response in mutant B-RAF melanoma cells.","display_name":"Downregulation of Noxa by RAF/MEK inhibition counteracts cell death response in mutant B-RAF melanoma cells.","publication_year":2012,"publication_date":"2012-01-01","ids":{"openalex":"https://openalex.org/W1566690127","mag":"1566690127","pmid":"https://pubmed.ncbi.nlm.nih.gov/23226618","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/3512187"},"language":"en","primary_location":{"id":"pmid:23226618","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/23226618","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"American journal of cancer research","raw_type":"Journal Article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3512187/","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5033787308","display_name":"Kevin J. Basile","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I149251103","display_name":"Thomas Jefferson University","ror":"https://ror.org/00ysqcn41","country_code":"US","type":"education","lineage":["https://openalex.org/I149251103"]},{"id":"https://openalex.org/I4210106595","display_name":"Sidney Kimmel Cancer Center","ror":"https://ror.org/010h6g454","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210106595"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kevin J Basile","raw_affiliation_strings":["Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University 233 South 10th Street, Philadelphia, PA 19107, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University 233 South 10th Street, Philadelphia, PA 19107, USA","institution_ids":["https://openalex.org/I149251103","https://openalex.org/I4210106595"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5062746446","display_name":"Andrew E. Aplin","orcid":"https://orcid.org/0000-0002-2734-3244","observed_orcids":["https://orcid.org/0000-0002-2734-3244"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Andrew E Aplin","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.6299,"has_fulltext":false,"cited_by_count":17,"citation_normalized_percentile":{"value":0.61124455,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":87,"max":96},"biblio":{"volume":"2","issue":"6","first_page":"726","last_page":"35"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":0.9945999979972839,"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/T11533","display_name":"Melanoma and MAPK Pathways","score":0.9945999979972839,"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/T10294","display_name":"Cell death mechanisms and regulation","score":0.00419999985024333,"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/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","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/pmaip1","display_name":"Noxa","score":0.996999979019165},{"id":"https://openalex.org/keywords/vemurafenib","display_name":"vemurafenib","score":0.9449999928474426},{"id":"https://openalex.org/keywords/melanoma","display_name":"melanoma","score":0.8169999718666077},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.7630000114440918},{"id":"https://openalex.org/keywords/bh3-only-proteins","display_name":"BH3-only proteins","score":0.9639999866485596},{"id":"https://openalex.org/keywords/mcl-1","display_name":"Mcl-1","score":0.9419999718666077},{"id":"https://openalex.org/keywords/bmf","display_name":"BMF","score":0.9409999847412109},{"id":"https://openalex.org/keywords/cell-cycle-arrest","display_name":"cell cycle arrest","score":0.6990000009536743},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.7820000052452087},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.8700000047683716}],"concepts":[{"id":"https://openalex.org/C2776131300","wikidata":"https://www.wikidata.org/wiki/Q423111","display_name":"Vemurafenib","level":4,"score":0.8919377326965332},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.7276896238327026},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.6331318616867065},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.5267581343650818},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.5162065625190735},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.4874017834663391},{"id":"https://openalex.org/C2780964509","wikidata":"https://www.wikidata.org/wiki/Q416975","display_name":"Dacarbazine","level":3,"score":0.46692582964897156},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.4451674818992615},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.42215728759765625},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.3945685923099518},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3735524117946625},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.30659395456314087},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.09154766798019409},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0},{"id":"https://openalex.org/C2994587330","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Metastatic melanoma","level":3,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":3,"locations":[{"id":"pmid:23226618","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/23226618","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"American journal of cancer research","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:3512187","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3512187/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Am J Cancer Res","raw_type":"Text"},{"id":"mag:1566690127","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/23226618","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"PubMed","raw_type":null}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:3512187","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3512187/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Am J Cancer Res","raw_type":"Text"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9391000270843506,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G4541587206","display_name":"B-RAF Regulation of the Cell Cycle in Melanoma","funder_award_id":"R01CA125103","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G6723851889","display_name":"ADHESION AND ERK SIGNALING IN MELANOMA","funder_award_id":"R01GM067893","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G9000897668","display_name":"Translational Research in Cancer","funder_award_id":"P30CA056036","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":32,"referenced_works":["https://openalex.org/W1509340652","https://openalex.org/W1982972087","https://openalex.org/W1984547206","https://openalex.org/W1985111376","https://openalex.org/W1990376228","https://openalex.org/W1990408342","https://openalex.org/W2003130292","https://openalex.org/W2003753849","https://openalex.org/W2009642188","https://openalex.org/W2014250484","https://openalex.org/W2015680924","https://openalex.org/W2017187984","https://openalex.org/W2027395744","https://openalex.org/W2031858847","https://openalex.org/W2032211985","https://openalex.org/W2032941109","https://openalex.org/W2033089897","https://openalex.org/W2043058822","https://openalex.org/W2050984994","https://openalex.org/W2080686146","https://openalex.org/W2085419794","https://openalex.org/W2097995306","https://openalex.org/W2100614336","https://openalex.org/W2106391833","https://openalex.org/W2106543129","https://openalex.org/W2112396699","https://openalex.org/W2127474966","https://openalex.org/W2128542677","https://openalex.org/W2134802480","https://openalex.org/W2141674733","https://openalex.org/W2163188200","https://openalex.org/W2168143310"],"related_works":["https://openalex.org/W15292524","https://openalex.org/W2167334545","https://openalex.org/W2018794234","https://openalex.org/W2315749053","https://openalex.org/W3120054634","https://openalex.org/W2142977207","https://openalex.org/W2334003094","https://openalex.org/W2129245282","https://openalex.org/W2020937386","https://openalex.org/W2000876153"],"abstract_inverted_index":{"FDA":[0],"approval":[1],"of":[2,56,133,157,185,193,199,210,250],"new":[3],"therapies":[4],"in":[5,53,201],"2011":[6],"has":[7,112],"greatly":[8],"expanded":[9],"the":[10,35,68,91,161,180,191,211,229,243,248],"treatment":[11],"options":[12],"for":[13],"metastatic":[14,29],"melanoma.":[15],"Patients":[16],"with":[17,34,76,190,203,225,234],"V600":[18],"mutant":[19],"v-raf":[20],"murine":[21],"sarcoma":[22],"viral":[23],"oncogene":[24],"homolog":[25],"B1":[26],"(B-RAF)":[27],"positive":[28],"melanoma":[30],"are":[31],"now":[32],"treated":[33,75],"RAF":[36],"inhibitor,":[37],"vemurafenib":[38,77],"(Zelboraf)":[39],"as":[40,141],"a":[41,100],"first":[42],"line":[43],"therapy.":[44],"Vemurafenib":[45],"decreases":[46],"tumor":[47,82],"size":[48],"by":[49],"at":[50,178],"least":[51],"30%":[52],"approximately":[54],"50%":[55],"patients":[57,74,86],"and":[58,62,84,106,145,159,182,187],"increases":[59],"progression-free":[60],"survival":[61,65],"overall":[63],"patient":[64],"compared":[66],"to":[67,79,90,103,109,155],"previous":[69],"standard-of-care,":[70],"dacarbazine.":[71],"However,":[72],"some":[73],"fail":[78],"show":[80,94,152],"significant":[81],"shrinkage,":[83],"most":[85],"who":[87],"initially":[88],"respond":[89],"drug":[92],"eventually":[93],"disease":[95],"progression.":[96,196],"Therefore,":[97],"there":[98],"is":[99,127,169,188],"clinical":[101],"need":[102],"improve":[104],"efficacy":[105,249],"prevent":[107],"resistance":[108],"vemurafenib.":[110],"It":[111],"been":[113],"previously":[114],"shown":[115],"that":[116,153,241],"cell":[117,194,207,220,231],"death":[118,232],"resulting":[119],"from":[120],"RAF/mitogen-activated":[121],"protein":[122,166,181],"kinase":[123,124],"(MEK)":[125],"inhibition":[126,192,205],"largely":[128],"dependent":[129],"on":[130],"increased":[131,235],"expression":[132,156,186,198],"pro-apoptotic,":[134,162],"Bcl-2":[135,146],"homology":[136],"domain":[137],"(BH3)-only":[138],"proteins,":[139],"such":[140],"Bcl-2-like":[142],"11":[143],"(Bim-EL)":[144],"modifying":[147],"factor":[148],"(Bmf).":[149],"Here,":[150],"we":[151],"contrary":[154],"Bim-EL":[158],"Bmf,":[160],"BH3-only":[163],"protein,":[164],"phorbol-12-myristate-13-acetate-induced":[165],"1":[167,223],"(Noxa),":[168],"strongly":[170],"downregulated":[171],"after":[172],"RAF/MEK":[173,204,251],"inhibition.":[174],"This":[175],"downregulation":[176],"occurs":[177],"both":[179],"mRNA":[183],"level":[184],"associated":[189,233],"cycle":[195],"Restoring":[197],"Noxa":[200,226,236],"combination":[202],"enhances":[206],"death.":[208],"Co-expression":[209],"pro-survival,":[212],"B-cell":[213],"CLL/lymphoma":[214],"2":[215],"(Bcl-2)":[216],"family":[217],"member,":[218],"myeloid":[219],"leukemia":[221],"sequence":[222],"(Mcl-1),":[224],"fully":[227],"mitigates":[228],"enhanced":[230],"expression.":[237],"These":[238],"data":[239],"indicate":[240],"manipulating":[242],"Noxa/Mcl-1":[244],"axis":[245],"may":[246],"enhance":[247],"inhibitors.":[252]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":2},{"year":2021,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":2},{"year":2017,"cited_by_count":2},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":2},{"year":2014,"cited_by_count":2},{"year":2013,"cited_by_count":2}],"updated_date":"2026-11-10T11:39:43.021295","created_date":"2016-06-24T00:00:00"}
