{"id":"https://openalex.org/W2809107888","doi":"https://doi.org/10.1093/neuonc/noy059.367","title":"LGG-26. TYPE II BRAF INHIBITOR TAK-580 SHOWS PROMISE FOR UPCOMING CLINAL TRIAL AS EVIDENCED BY SINGLE PATIENT IND STUDY","display_name":"LGG-26. TYPE II BRAF INHIBITOR TAK-580 SHOWS PROMISE FOR UPCOMING CLINAL TRIAL AS EVIDENCED BY SINGLE PATIENT IND STUDY","publication_year":2018,"publication_date":"2018-06-01","ids":{"openalex":"https://openalex.org/W2809107888","doi":"https://doi.org/10.1093/neuonc/noy059.367","mag":"2809107888"},"language":"en","primary_location":{"id":"doi:10.1093/neuonc/noy059.367","doi":"https://doi.org/10.1093/neuonc/noy059.367","is_oa":false,"landing_page_url":"https://doi.org/10.1093/neuonc/noy059.367","pdf_url":null,"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":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6012010","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5090423495","display_name":"Karen D. Wright","orcid":"https://orcid.org/0000-0002-9578-1545","observed_orcids":["https://orcid.org/0000-0002-9578-1545"]},"institutions":[{"id":"https://openalex.org/I1288882113","display_name":"Boston Children's Hospital","ror":"https://ror.org/00dvg7y05","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1288882113"]},{"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":"Karen D Wright","raw_affiliation_strings":["Boston Children\u2019s Hospital, Boston, MA, USA","Dana-Farber Cancer Institute, Boston, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Boston Children\u2019s Hospital, Boston, MA, USA","institution_ids":["https://openalex.org/I1288882113"]},{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Mary Ann Zimmerman","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1288882113","display_name":"Boston Children's Hospital","ror":"https://ror.org/00dvg7y05","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1288882113"]},{"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":"Mary Ann Zimmerman","raw_affiliation_strings":["Boston Children\u2019s Hospital, Boston, MA, USA","Dana-Farber Cancer Institute, Boston, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Boston Children\u2019s Hospital, Boston, MA, USA","institution_ids":["https://openalex.org/I1288882113"]},{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046254702","display_name":"Elizabeth Fine","orcid":"https://orcid.org/0000-0002-4812-5924","observed_orcids":["https://orcid.org/0000-0002-4812-5924"]},"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":"Elizabeth Fine","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/A5002072146","display_name":"Tristan Aspri","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":"Tristan Aspri","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/A5060208068","display_name":"Mark W. Kieran","orcid":"https://orcid.org/0000-0003-2184-7692","observed_orcids":["https://orcid.org/0000-0003-2184-7692"]},"institutions":[{"id":"https://openalex.org/I1288882113","display_name":"Boston Children's Hospital","ror":"https://ror.org/00dvg7y05","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1288882113"]},{"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":"Mark W Kieran","raw_affiliation_strings":["Boston Children\u2019s Hospital, Boston, MA, USA","Dana-Farber Cancer Institute, Boston, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Boston Children\u2019s Hospital, Boston, MA, USA","institution_ids":["https://openalex.org/I1288882113"]},{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5068793931","display_name":"Susan N Chi","orcid":"https://orcid.org/0000-0001-7753-878X","observed_orcids":["https://orcid.org/0000-0001-7753-878X"]},"institutions":[{"id":"https://openalex.org/I1288882113","display_name":"Boston Children's Hospital","ror":"https://ror.org/00dvg7y05","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1288882113"]},{"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":"Susan Chi","raw_affiliation_strings":["Boston Children\u2019s Hospital, Boston, MA, USA","Dana-Farber Cancer Institute, Boston, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Boston Children\u2019s Hospital, Boston, MA, USA","institution_ids":["https://openalex.org/I1288882113"]},{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA","institution_ids":["https://openalex.org/I4210117453"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5132,"currency":"USD","value_usd":5132},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":9,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"20","issue":"suppl_2","first_page":"i110","last_page":"i110"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.9340999722480774,"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":0.9340999722480774,"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/T11533","display_name":"Melanoma and MAPK Pathways","score":0.023800000548362732,"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/T11173","display_name":"Neurofibromatosis and Schwannoma Cases","score":0.004699999932199717,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Neurology"},"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/pediatric-low-grade-glioma","display_name":"pediatric low-grade glioma","score":0.9909999966621399},{"id":"https://openalex.org/keywords/ras-raf-pathway","display_name":"RAS/RAF pathway","score":0.8149999976158142},{"id":"https://openalex.org/keywords/braf-v600e-mutation","display_name":"BRAF V600E mutation","score":0.9649999737739563},{"id":"https://openalex.org/keywords/kiaa1549-braf-fusion","display_name":"KIAA1549-BRAF fusion","score":0.9419999718666077},{"id":"https://openalex.org/keywords/mek-inhibition","display_name":"MEK inhibition","score":0.7480000257492065},{"id":"https://openalex.org/keywords/drug-tolerability","display_name":"drug tolerability","score":0.6019999980926514},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.9269999861717224},{"id":"https://openalex.org/keywords/pediatric-oncology-drug-development","display_name":"pediatric oncology drug development","score":0.49300000071525574}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.7859770059585571},{"id":"https://openalex.org/C2778570526","wikidata":"https://www.wikidata.org/wiki/Q653197","display_name":"Rash","level":2,"score":0.5895329117774963},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.5576956868171692},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.5011923313140869},{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.4968433678150177},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.47780996561050415},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4705412983894348},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.44679877161979675},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.42261773347854614},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.41158565878868103},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3880195617675781},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.1321428418159485},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.08830556273460388}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1093/neuonc/noy059.367","doi":"https://doi.org/10.1093/neuonc/noy059.367","is_oa":false,"landing_page_url":"https://doi.org/10.1093/neuonc/noy059.367","pdf_url":null,"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:pubmedcentral.nih.gov:6012010","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6012010","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":"pmh:oai:pubmedcentral.nih.gov:6012010","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6012010","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"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":1.0,"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/W2429247155","https://openalex.org/W2576797066","https://openalex.org/W4380362753","https://openalex.org/W2602580724","https://openalex.org/W2159517181","https://openalex.org/W2808988165","https://openalex.org/W4406130256","https://openalex.org/W4399787313","https://openalex.org/W2620179955","https://openalex.org/W2199948760"],"abstract_inverted_index":{"Abnormal":[0],"signaling":[1],"of":[2,42,46,134,161,176,210,237],"the":[3,144,155,213,232],"RAS/RAF":[4],"pathway":[5,246],"predominates":[6],"in":[7,51,64,226],"pediatric":[8],"low-grade":[9,15],"gliomas":[10,16],"(PLGGs).":[11],"Most":[12],"(85%)":[13],"non-NF1":[14],"have":[17],"RAS-independent":[18],"BRAF":[19,39,58,219],"activation,":[20],"either":[21],"due":[22],"to":[23,118,151,154],"KIAA1549:BRAF":[24],"truncated":[25,59],"fusion":[26,60],"duplication":[27],"or":[28,189],"V600E":[29],"point":[30,55,220],"mutation.":[31],"We":[32,83],"previously":[33],"identified":[34],"two":[35],"different":[36,109],"type":[37],"II":[38],"inhibitors":[40],"capable":[41],"inhibiting":[43,217],"downstream":[44],"activation":[45],"pERK":[47],"and":[48,57,78,105,141,147,168,186,202,216,222,243],"tumor":[49,163],"progression":[50],"vivo":[52,77],"for":[53,90,239],"multiple":[54],"mutations":[56,221],"forms.":[61],"One":[62],"compound,":[63],"particular,":[65],"known":[66],"as":[67],"TAK-580":[68,180,205,238],"was":[69,98,123,132,181],"active":[70],"on":[71,126,138],"authentic":[72],"human":[73],"PLGG":[74],"cells":[75],"ex":[76],"showed":[79],"excellent":[80],"CNS":[81],"penetration.":[82],"conducted":[84],"a":[85,91,127,207],"single":[86],"patient":[87,92,169],"IND":[88],"study":[89],"with":[93,107,241],"refractory,":[94],"progressive":[95],"LGG.":[96],"Patient":[97],"initially":[99],"diagnosed":[100],"at":[101],"age":[102,114],"2":[103],"years":[104,116],"treated":[106],"9":[108],"chemotherapy":[110],"regimens":[111],"up":[112],"until":[113],"15":[115],"prior":[117],"starting":[119],"TAK-580.":[120,179],"Study":[121],"drug":[122],"begun":[124],"orally":[125],"QOD":[128],"schedule;":[129],"one":[130],"cycle":[131,175],"comprised":[133],"28":[135],"days.":[136],"Based":[137],"both":[139,218],"tolerance":[140],"pharmacokinetic":[142],"analyses,":[143],"treatment":[145],"schedule":[146],"dosing":[148,157],"were":[149],"adjusted":[150],"weekly,":[152],"comparable":[153],"adult":[156],"schedule.":[158],"MR":[159],"imaging":[160],"her":[162,173],"burden":[164],"has":[165,170],"remained":[166],"stable,":[167],"recently":[171],"started":[172],"33rd":[174],"once":[177],"weekly":[178],"well":[182],"tolerated.":[183],"Grade":[184],"3":[185],"4":[187],"likely":[188],"possibly":[190],"related":[191],"toxicities":[192],"included":[193],"acneiform":[194],"rash,":[195],"hyperglycemia,":[196],"elevated":[197,200],"creatinine":[198],"kinase,":[199],"ALT":[201],"decreased":[203],"phosphorus.":[204],"posess":[206],"unique":[208],"mechanism":[209],"action":[211],"targeting":[212],"BRAF/MEK":[214],"complex":[215],"common":[223],"structural":[224],"abnormalities":[225],"PLGGs.":[227],"These":[228],"initial":[229],"results":[230],"support":[231],"upcoming":[233],"phase":[234],"I/0/II":[235],"trial":[236],"children":[240],"LGG":[242],"other":[244],"RAS/RAF/MEK/ERK":[245],"activated":[247],"tumors.":[248]},"counts_by_year":[{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":3},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":3}],"updated_date":"2026-10-30T12:39:25.321706","created_date":"2018-06-29T00:00:00"}