{"id":"https://openalex.org/W4242768529","doi":"https://doi.org/10.1093/neuonc/nox083.241","title":"TRTH-31. EFFECTS OF TORC1/2 INHIBITOR MLN0128 ALONE AND IN COMBINATION WITH MEK INHIBITION IN BRAF MUTATED GLIOMA CELLS","display_name":"TRTH-31. EFFECTS OF TORC1/2 INHIBITOR MLN0128 ALONE AND IN COMBINATION WITH MEK INHIBITION IN BRAF MUTATED GLIOMA CELLS","publication_year":2017,"publication_date":"2017-05-31","ids":{"openalex":"https://openalex.org/W4242768529","doi":"https://doi.org/10.1093/neuonc/nox083.241"},"language":"en","primary_location":{"id":"doi:10.1093/neuonc/nox083.241","doi":"https://doi.org/10.1093/neuonc/nox083.241","is_oa":true,"landing_page_url":"https://doi.org/10.1093/neuonc/nox083.241","pdf_url":"https://academic.oup.com/neuro-oncology/article-pdf/19/suppl_4/iv58/17643142/nox083.241.pdf","source":{"id":"https://openalex.org/S106908163","display_name":"Neuro-Oncology","issn_l":"1522-8517","issn":["1522-8517","1523-5866"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neuro-Oncology","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://academic.oup.com/neuro-oncology/article-pdf/19/suppl_4/iv58/17643142/nox083.241.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5103236468","display_name":"Sabine Mueller","orcid":"https://orcid.org/0000-0002-8216-9357","observed_orcids":["https://orcid.org/0000-0002-8216-9357","https://orcid.org/0000-0002-3452-5150"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sabine Mueller","raw_affiliation_strings":["University of California, San Francisco, San Francisco, CA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California, San Francisco, San Francisco, CA, USA,","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001129819","display_name":"Rogier Dirk","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rogier Dirk","raw_affiliation_strings":["VA University Medical Center, Amsterdam, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"VA University Medical Center, Amsterdam, The Netherlands","institution_ids":[]}]},{"author_position":"middle","author":{"id":null,"display_name":"Xiaodong Yang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Xiaodong Yang","raw_affiliation_strings":["University of California, San Francisco, San Francisco, CA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California, San Francisco, San Francisco, CA, USA,","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Steve DuBois","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Steve DuBois","raw_affiliation_strings":["Dana Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015199029","display_name":"Angela Jae Waanders","orcid":"https://orcid.org/0000-0002-0571-2889","observed_orcids":["https://orcid.org/0000-0002-0571-2889"]},"institutions":[{"id":"https://openalex.org/I1335321130","display_name":"Children's Hospital of Philadelphia","ror":"https://ror.org/01z7r7q48","country_code":"US","type":"funder","lineage":["https://openalex.org/I1335321130"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Angela Waanders","raw_affiliation_strings":["Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA,","institution_ids":["https://openalex.org/I1335321130"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086085263","display_name":"Adam Cain Resnick","orcid":"https://orcid.org/0000-0003-0436-4189","observed_orcids":["https://orcid.org/0000-0003-0436-4189"]},"institutions":[{"id":"https://openalex.org/I1335321130","display_name":"Children's Hospital of Philadelphia","ror":"https://ror.org/01z7r7q48","country_code":"US","type":"funder","lineage":["https://openalex.org/I1335321130"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Adam Resnick","raw_affiliation_strings":["Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA,","institution_ids":["https://openalex.org/I1335321130"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073603294","display_name":"William A. Weiss","orcid":"https://orcid.org/0000-0003-2230-9132","observed_orcids":["https://orcid.org/0000-0003-2230-9132"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"William Weiss","raw_affiliation_strings":["University of California, San Francisco, San Francisco, CA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California, San Francisco, San Francisco, CA, USA,","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5085032736","display_name":"Daphne Adele Haas-Kogan","orcid":"https://orcid.org/0000-0002-2378-4800","observed_orcids":["https://orcid.org/0000-0002-2378-4800"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Daphne Haas-Kogan","raw_affiliation_strings":["Dana Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5132,"currency":"USD","value_usd":5132},"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"19","issue":"suppl_4","first_page":"iv58","last_page":"iv58"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.8779000043869019,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.8779000043869019,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics"},"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.0640999972820282,"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/T12049","display_name":"Tuberous Sclerosis Complex Research","score":0.00800000037997961,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"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/mln0128","display_name":"MLN0128","score":0.9700000286102295},{"id":"https://openalex.org/keywords/mtorc1-2-inhibition","display_name":"mTORC1/2 inhibition","score":0.7739999890327454},{"id":"https://openalex.org/keywords/mek-inhibition","display_name":"MEK inhibition","score":0.7639999985694885},{"id":"https://openalex.org/keywords/braf-v600e-mutation","display_name":"BRAF V600E mutation","score":0.9350000023841858},{"id":"https://openalex.org/keywords/pediatric-low-grade-glioma","display_name":"pediatric low-grade glioma","score":0.9829999804496765},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.7620000243186951},{"id":"https://openalex.org/keywords/plx4720","display_name":"PLX4720","score":0.9039999842643738},{"id":"https://openalex.org/keywords/selumetinib","display_name":"selumetinib","score":0.953000009059906},{"id":"https://openalex.org/keywords/trametinib","display_name":"trametinib","score":0.9570000171661377},{"id":"https://openalex.org/keywords/everolimus","display_name":"everolimus","score":0.9810000061988831},{"id":"https://openalex.org/keywords/akt-signaling","display_name":"Akt signaling","score":0.7129999995231628},{"id":"https://openalex.org/keywords/erk-signaling","display_name":"ERK signaling","score":0.8109999895095825},{"id":"https://openalex.org/keywords/drug-synergy","display_name":"drug synergy","score":0.5630000233650208},{"id":"https://openalex.org/keywords/antiproliferative-activity","display_name":"antiproliferative activity","score":0.7590000033378601},{"id":"https://openalex.org/keywords/mtor","display_name":"mTOR","score":0.3659999966621399}],"concepts":[{"id":"https://openalex.org/C2779699572","wikidata":"https://www.wikidata.org/wiki/Q421052","display_name":"Everolimus","level":2,"score":0.7618535757064819},{"id":"https://openalex.org/C98490376","wikidata":"https://www.wikidata.org/wiki/Q14876060","display_name":"mTORC1","level":4,"score":0.6653493642807007},{"id":"https://openalex.org/C2781249067","wikidata":"https://www.wikidata.org/wiki/Q17142288","display_name":"MEK inhibitor","level":4,"score":0.570868968963623},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.5312312245368958},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.481302410364151},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.47319623827934265},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.4727025032043457},{"id":"https://openalex.org/C2778227246","wikidata":"https://www.wikidata.org/wiki/Q1365309","display_name":"Glioma","level":2,"score":0.4108467698097229},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.376809686422348},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.3422256112098694},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3276185393333435},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.27639997005462646},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2128216028213501},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.17707118391990662},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.1741011142730713},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.08619928359985352},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.05230975151062012}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.1093/neuonc/nox083.241","doi":"https://doi.org/10.1093/neuonc/nox083.241","is_oa":true,"landing_page_url":"https://doi.org/10.1093/neuonc/nox083.241","pdf_url":"https://academic.oup.com/neuro-oncology/article-pdf/19/suppl_4/iv58/17643142/nox083.241.pdf","source":{"id":"https://openalex.org/S106908163","display_name":"Neuro-Oncology","issn_l":"1522-8517","issn":["1522-8517","1523-5866"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neuro-Oncology","raw_type":"journal-article"},{"id":"pmh:oai:europepmc.org:4928596","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5475214","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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":null,"raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:5475214","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5475214","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":"Neuro Oncol","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1093/neuonc/nox083.241","doi":"https://doi.org/10.1093/neuonc/nox083.241","is_oa":true,"landing_page_url":"https://doi.org/10.1093/neuonc/nox083.241","pdf_url":"https://academic.oup.com/neuro-oncology/article-pdf/19/suppl_4/iv58/17643142/nox083.241.pdf","source":{"id":"https://openalex.org/S106908163","display_name":"Neuro-Oncology","issn_l":"1522-8517","issn":["1522-8517","1523-5866"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neuro-Oncology","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4242768529.pdf","grobid_xml":"https://content.openalex.org/works/W4242768529.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2767882653","https://openalex.org/W2063878146","https://openalex.org/W2940675347","https://openalex.org/W2403601567","https://openalex.org/W2159517181","https://openalex.org/W6987546664","https://openalex.org/W2809230487","https://openalex.org/W2996449472","https://openalex.org/W2886882149","https://openalex.org/W2956066363"],"abstract_inverted_index":{"INTRODUCTION:":[0],"MLN0128,":[1,61],"a":[2,164,280],"second-generation":[3],"ATP-competitive":[4],"pan-mTOR":[5],"kinase":[6],"inhibitor,":[7],"acts":[8],"on":[9],"both":[10],"mTORC1":[11],"and":[12,21,26,51,67,72,134,194,222,285],"mTORC2.":[13],"We":[14,37],"investigated":[15],"the":[16,157,185],"effects":[17,83,110,202,240],"of":[18,31,54,120,131,143,159,218,220,230],"MLN0128":[19,104,127,160,193,223,236,266,274],"monotherapy":[20,105,289],"in":[22,29,100,114,153,166,169,174,209,244,263,279],"combination":[23,229],"with":[24,126,138,147,192,241,269,273],"MEK":[25,68,145,242],"BRAFV600E":[27,44,63,177,186,247,281],"inhibition":[28,146,243],"models":[30],"pediatric":[32],"low-grade":[33],"glioma":[34,40,283],"(PLGG).":[35],"METHODS:":[36],"used":[38,97],"human":[39],"cell":[41],"lines":[42,118],"expressing":[43],"(AM38),":[45],"wild-type":[46,252],"BRAF":[47,121,251],"(LN229,":[48],"TN98,":[49],"SF188)":[50],"isogenic":[52],"systems":[53],"KIAA1549:BRAF-expressing":[55],"NIH3T3":[56],"cells.":[57],"Signaling":[58],"inhibitors":[59,70],"included":[60],"everolimus,":[62],"specific":[64,69],"inhibitor":[65],"PLX4720,":[66],"AZD6244":[71,148,162,197],"GSK1120212.":[73],"Cell":[74],"proliferation":[75],"was":[76,96],"determined":[77],"using":[78,86],"an":[79],"ATP-based":[80],"assay.":[81],"Biochemical":[82],"were":[84],"assessed":[85],"western":[87],"blot":[88],"analysis.":[89],"The":[90],"DBTRG":[91],"(BRAFV600E)":[92],"xenograft":[93],"mouse":[94],"model":[95,284],"to":[98,112,129,161,199,225,261,288],"assess":[99],"vivo":[101,213],"efficacy.":[102],"RESULTS:":[103],"demonstrates":[106],"more":[107],"potent":[108],"anti-proliferative":[109,201],"compared":[111,224],"everolimus":[113,139,233,291],"all":[115,154],"tested":[116],"PLGG":[117],"independent":[119],"status.":[122],"As":[123],"expected,":[124],"treatment":[125,137,191],"leads":[128,198],"down-regulation":[130],"p-AKT,":[132],"p-S6":[133],"p-4EBP1,":[135],"whereas":[136],"only":[140],"reduces":[141],"expression":[142,152,168,176],"p-S6.":[144],"effectively":[149],"decreases":[150],"p-ERK":[151,167,264],"lines;":[155],"however,":[156],"addition":[158],"causes":[163],"rebound":[165,262],"BRAFWT":[170,210],"gliomas":[171,175,245],"but":[172,203],"not":[173,207,257],"or":[178,187,196,228,248,290],"KIAA1549:BRAF":[179,188],"alterations.":[180],"In":[181,212,250],"cells":[182,253],"carrying":[183],"either":[184],"alteration,":[189],"combined":[190,268],"GSK1120212":[195],"synergistic":[200,238],"such":[204,254],"synergy":[205,255],"is":[206,256,267,286],"evident":[208],"gliomas.":[211],"studies":[214],"show":[215],"superior":[216,287],"efficacy":[217],"combinations":[219],"PLX4720":[221,231,276,293],"monotherapies":[226],"(p<0.02)":[227],"+":[232,275,292],"(p=0.03).":[234],"CONCLUSION:":[235],"displays":[237],"anti-neoplastic":[239],"bearing":[246],"KIAA1549:BRAF.":[249],"present,":[258],"potentially":[259],"due":[260],"when":[265],"AZD6244.":[270],"Combination":[271],"therapy":[272],"prolongs":[277],"survival":[278],"mutant":[282],"combination.":[294]},"counts_by_year":[],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2022-05-12T00:00:00"}