{"id":"https://openalex.org/W1852944023","doi":"https://doi.org/10.1158/1535-7163.mct-15-0136-t","title":"Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors","display_name":"Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors","publication_year":2015,"publication_date":"2015-09-08","ids":{"openalex":"https://openalex.org/W1852944023","doi":"https://doi.org/10.1158/1535-7163.mct-15-0136-t","mag":"1852944023","pmid":"https://pubmed.ncbi.nlm.nih.gov/26351322","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/4674359"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.mct-15-0136-t","doi":"https://doi.org/10.1158/1535-7163.mct-15-0136-t","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1535-7163.mct-15-0136-t","pdf_url":null,"source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","poland-140","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":"Molecular Cancer Therapeutics","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4674359","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5034616567","display_name":"Steven R. Whittaker","orcid":"https://orcid.org/0000-0001-9062-7947","observed_orcids":["https://orcid.org/0000-0001-9062-7947"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]},{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]},{"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":["GB","US"],"is_corresponding":false,"raw_author_name":"Steven R. Whittaker","raw_affiliation_strings":["1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts","2The Broad Institute, Cambridge, Massachusetts","3Division of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts","institution_ids":["https://openalex.org/I4210117453"]},{"raw_affiliation_string":"2The Broad Institute, Cambridge, Massachusetts","institution_ids":["https://openalex.org/I107606265"]},{"raw_affiliation_string":"3Division of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060190177","display_name":"Glenn S. Cowley","orcid":"https://orcid.org/0000-0002-0526-0616","observed_orcids":["https://orcid.org/0000-0002-0526-0616"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Glenn S. Cowley","raw_affiliation_strings":["2The Broad Institute, Cambridge, Massachusetts"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2The Broad Institute, Cambridge, Massachusetts","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103680899","display_name":"Steve Wagner","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Steve Wagner","raw_affiliation_strings":["3Division of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Division of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112904471","display_name":"Flora Luo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]},{"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":"Flora Luo","raw_affiliation_strings":["1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts","2The Broad Institute, Cambridge, Massachusetts"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts","institution_ids":["https://openalex.org/I4210117453"]},{"raw_affiliation_string":"2The Broad Institute, Cambridge, Massachusetts","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086771961","display_name":"David E. Root","orcid":"https://orcid.org/0000-0001-5122-861X","observed_orcids":["https://orcid.org/0000-0001-5122-861X","https://orcid.org/0000-0003-0096-4830"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David E. Root","raw_affiliation_strings":["2The Broad Institute, Cambridge, Massachusetts"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2The Broad Institute, Cambridge, Massachusetts","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5055048393","display_name":"Levi A. Garraway","orcid":"https://orcid.org/0000-0003-3739-0471","observed_orcids":["https://orcid.org/0000-0003-3739-0471"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]},{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"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":true,"raw_author_name":"Levi A. Garraway","raw_affiliation_strings":["1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts","2The Broad Institute, Cambridge, Massachusetts","4Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts","5Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts","institution_ids":["https://openalex.org/I4210117453"]},{"raw_affiliation_string":"2The Broad Institute, Cambridge, Massachusetts","institution_ids":["https://openalex.org/I107606265"]},{"raw_affiliation_string":"4Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts","institution_ids":["https://openalex.org/I4210117453"]},{"raw_affiliation_string":"5Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts","institution_ids":["https://openalex.org/I1283280774","https://openalex.org/I136199984"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5055048393"],"corresponding_institution_ids":["https://openalex.org/I107606265","https://openalex.org/I1283280774","https://openalex.org/I136199984","https://openalex.org/I4210117453"],"apc_list":null,"apc_paid":null,"fwci":3.3023,"has_fulltext":false,"cited_by_count":75,"citation_normalized_percentile":{"value":0.93542737,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":96,"max":100},"biblio":{"volume":"14","issue":"12","first_page":"2700","last_page":"2711"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":0.9937000274658203,"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":0.9937000274658203,"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":0.002899999963119626,"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/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.0010999999940395355,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/pan-raf-inhibitor","display_name":"pan-RAF inhibitor","score":0.8360000252723694},{"id":"https://openalex.org/keywords/mek-inhibitors","display_name":"MEK inhibitors","score":0.9919999837875366},{"id":"https://openalex.org/keywords/raf-inhibitor-resistance","display_name":"RAF inhibitor resistance","score":0.8460000157356262},{"id":"https://openalex.org/keywords/braf-mutant-melanoma","display_name":"BRAF-mutant melanoma","score":0.8769999742507935},{"id":"https://openalex.org/keywords/braf-mutant-colorectal-cancer","display_name":"BRAF-mutant colorectal cancer","score":0.9980000257492065},{"id":"https://openalex.org/keywords/raf-1","display_name":"Raf-1","score":0.8679999709129333},{"id":"https://openalex.org/keywords/plx4720","display_name":"PLX4720","score":0.9259999990463257},{"id":"https://openalex.org/keywords/dabrafenib","display_name":"dabrafenib","score":0.968999981880188},{"id":"https://openalex.org/keywords/mapk-signaling","display_name":"MAPK signaling","score":0.8539999723434448},{"id":"https://openalex.org/keywords/kras-mutation","display_name":"KRAS mutation","score":0.9599999785423279},{"id":"https://openalex.org/keywords/receptor-tyrosine-kinase-signaling","display_name":"receptor tyrosine kinase signaling","score":0.7020000219345093},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.6150000095367432},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.6169999837875366},{"id":"https://openalex.org/keywords/enhancer-screen","display_name":"enhancer screen","score":0.7260000109672546}],"concepts":[{"id":"https://openalex.org/C2781187634","wikidata":"https://www.wikidata.org/wiki/Q20969980","display_name":"KRAS","level":4,"score":0.7712205052375793},{"id":"https://openalex.org/C2781249067","wikidata":"https://www.wikidata.org/wiki/Q17142288","display_name":"MEK inhibitor","level":4,"score":0.7472099661827087},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5989342927932739},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.53925621509552},{"id":"https://openalex.org/C2778472372","wikidata":"https://www.wikidata.org/wiki/Q7833138","display_name":"Trametinib","level":4,"score":0.48590484261512756},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.4695599377155304},{"id":"https://openalex.org/C2779707156","wikidata":"https://www.wikidata.org/wiki/Q5611758","display_name":"Growth inhibition","level":3,"score":0.46489375829696655},{"id":"https://openalex.org/C2778830669","wikidata":"https://www.wikidata.org/wiki/Q3011604","display_name":"Dabrafenib","level":5,"score":0.44717785716056824},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.42880022525787354},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.39073896408081055},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.34161680936813354},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.3397985100746155},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.32679682970046997},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.29569903016090393},{"id":"https://openalex.org/C2776131300","wikidata":"https://www.wikidata.org/wiki/Q423111","display_name":"Vemurafenib","level":4,"score":0.2085997760295868},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.1315266489982605},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.09892204403877258},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.07580474019050598},{"id":"https://openalex.org/C2994587330","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Metastatic melanoma","level":3,"score":0.0}],"mesh":[{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007211","descriptor_name":"Indoles","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013449","descriptor_name":"Sulfonamides","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D015179","descriptor_name":"Colorectal Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D015179","descriptor_name":"Colorectal Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D015179","descriptor_name":"Colorectal Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D016283","descriptor_name":"Proto-Oncogene Proteins p21(ras)","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D017209","descriptor_name":"Apoptosis","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D019008","descriptor_name":"Drug Resistance, Neoplasm","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D020930","descriptor_name":"MAP Kinase Kinase Kinases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D020930","descriptor_name":"MAP Kinase Kinase Kinases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D020935","descriptor_name":"MAP Kinase Signaling System","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D048490","descriptor_name":"raf Kinases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D048490","descriptor_name":"raf Kinases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1158/1535-7163.mct-15-0136-t","doi":"https://doi.org/10.1158/1535-7163.mct-15-0136-t","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1535-7163.mct-15-0136-t","pdf_url":null,"source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","poland-140","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":"Molecular Cancer Therapeutics","raw_type":"journal-article"},{"id":"pmid:26351322","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/26351322","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":"Molecular cancer therapeutics","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:4674359","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4674359","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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Mol Cancer Ther","raw_type":"Text"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:4674359","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4674359","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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Mol Cancer Ther","raw_type":"Text"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9391000270843506}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1119066253","display_name":"Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer","funder_award_id":"P50CA127003","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G485996810","display_name":"Defining Melanoma Therapeutic Avenues by Integrative Functional Genomics","funder_award_id":"DP2OD002750","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G5343362609","display_name":"High-Throughput Tumor Genomic Profiling by Massively Parallel Sequencing","funder_award_id":"R33CA155554","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G9000900783","display_name":"Targetable epigenetic and transcriptional mechanisms in melanoma thatshape the microenvironment","funder_award_id":"P01CA163222","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":56,"referenced_works":["https://openalex.org/W1554484942","https://openalex.org/W1592483428","https://openalex.org/W1844240163","https://openalex.org/W1888056807","https://openalex.org/W1965440903","https://openalex.org/W1970174659","https://openalex.org/W1971875278","https://openalex.org/W1971947883","https://openalex.org/W1980427440","https://openalex.org/W1985928174","https://openalex.org/W1999025555","https://openalex.org/W2004295816","https://openalex.org/W2009642188","https://openalex.org/W2014881369","https://openalex.org/W2017187984","https://openalex.org/W2032210521","https://openalex.org/W2032211985","https://openalex.org/W2033185023","https://openalex.org/W2041255253","https://openalex.org/W2043398720","https://openalex.org/W2046514328","https://openalex.org/W2049992341","https://openalex.org/W2050206485","https://openalex.org/W2051165598","https://openalex.org/W2055624262","https://openalex.org/W2058554042","https://openalex.org/W2065909963","https://openalex.org/W2080534618","https://openalex.org/W2081038787","https://openalex.org/W2091334045","https://openalex.org/W2100614336","https://openalex.org/W2110682589","https://openalex.org/W2119081353","https://openalex.org/W2121539092","https://openalex.org/W2128339707","https://openalex.org/W2128542677","https://openalex.org/W2130159206","https://openalex.org/W2133523341","https://openalex.org/W2141674733","https://openalex.org/W2141787711","https://openalex.org/W2142682969","https://openalex.org/W2149312624","https://openalex.org/W2149576348","https://openalex.org/W2149662085","https://openalex.org/W2152171197","https://openalex.org/W2154196978","https://openalex.org/W2155381255","https://openalex.org/W2158416296","https://openalex.org/W2159856482","https://openalex.org/W2160378889","https://openalex.org/W2166262263","https://openalex.org/W2168420784","https://openalex.org/W2474250696","https://openalex.org/W2589319728","https://openalex.org/W6639599763","https://openalex.org/W6721158425"],"related_works":["https://openalex.org/W2405035841","https://openalex.org/W2315978372","https://openalex.org/W4243460376","https://openalex.org/W1527410143","https://openalex.org/W2091334045","https://openalex.org/W2805631082","https://openalex.org/W2739500506","https://openalex.org/W2299664064","https://openalex.org/W2499892494","https://openalex.org/W1980608547"],"abstract_inverted_index":{"RAF":[0,33,43,73,139],"and":[1,110,118,184,199,205,215,225],"MEK":[2,103,111,147,185,200,216],"inhibitors":[3,98,112,148,162],"are":[4],"effective":[5],"in":[6,11,30,99,116,167,172,188],"BRAF-mutant":[7,12],"melanoma":[8,117],"but":[9],"not":[10,150],"colorectal":[13,35,119],"cancer.":[14],"To":[15],"gain":[16],"additional":[17],"insights":[18],"into":[19],"this":[20],"difference,":[21],"we":[22],"performed":[23],"a":[24,31,84,102,164,219],"genome-scale":[25],"pooled":[26],"shRNA":[27],"enhancer":[28],"screen":[29],"BRAF-mutant,":[32],"inhibitor-resistant":[34],"cancer":[36,120],"cell":[37,121],"line":[38],"exposed":[39],"to":[40,70,174,208],"the":[41,51,71,94,106,175,189],"selective":[42,72,138],"inhibitor":[44,74],"PLX4720.":[45],"We":[46],"identified":[47],"multiple":[48],"genes":[49],"along":[50],"receptor":[52],"tyrosine":[53],"kinase":[54,57],"(RTK)/mitogen-activated":[55],"protein":[56],"(MAPK)":[58],"signaling":[59],"axis":[60],"that,":[61],"when":[62],"suppressed,":[63],"either":[64],"genetically":[65],"or":[66,132,144],"pharmacologically,":[67],"sensitized":[68],"cells":[69],"through":[75],"sustained":[76],"inhibition":[77,157,186,201,217],"of":[78,87,96,108,137,158,191],"MAPK":[79],"signaling.":[80],"Strikingly,":[81],"CRAF":[82,159],"was":[83],"key":[85,165],"mediator":[86],"resistance":[88,207],"that":[89,156],"could":[90],"be":[91],"overcome":[92,203],"by":[93,160],"use":[95],"pan-RAF":[97,109,161,183,198,214],"combination":[100,107],"with":[101,123,146,179],"inhibitor.":[104],"Furthermore,":[105],"displayed":[113],"strong":[114],"synergy":[115],"lines":[122],"RAS-activating":[124],"events":[125],"such":[126,141,152],"as":[127,142,218],"RTK":[128],"activation,":[129],"KRAS":[130],"mutation,":[131],"NF1":[133],"loss-of-function":[134],"mutations.":[135],"Combinations":[136],"inhibitors,":[140],"PLX4720":[143],"dabrafenib,":[145],"did":[149],"incur":[151],"profound":[153],"synergy,":[154],"suggesting":[155],"plays":[163],"role":[166],"determining":[168],"cellular":[169],"response.":[170],"Importantly,":[171],"contrast":[173],"modest":[176],"activity":[177],"seen":[178],"single-agent":[180,209],"treatment,":[181],"dual":[182,213],"results":[187],"induction":[190],"apoptosis,":[192],"greatly":[193],"enhancing":[194],"efficacy.":[195],"Notably,":[196],"combined":[197],"can":[202],"intrinsic":[204],"acquired":[206],"RAF/MEK":[210],"inhibition,":[211],"supporting":[212],"novel":[220],"therapeutic":[221],"strategy":[222],"for":[223],"BRAF-":[224],"KRAS-mutant":[226],"cancers.":[227]},"counts_by_year":[{"year":2026,"cited_by_count":5},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":8},{"year":2023,"cited_by_count":5},{"year":2022,"cited_by_count":5},{"year":2021,"cited_by_count":4},{"year":2020,"cited_by_count":6},{"year":2019,"cited_by_count":11},{"year":2018,"cited_by_count":6},{"year":2017,"cited_by_count":8},{"year":2016,"cited_by_count":14}],"updated_date":"2026-11-05T12:25:35.769452","created_date":"2016-06-24T00:00:00"}