{"id":"https://openalex.org/W2312980366","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-419","title":"Abstract LB-419: An in-frame deletion in the N-terminal regulatory domain of BRAF(V600E) causes resistance to the RAF inhibitor PLX4032","display_name":"Abstract LB-419: An in-frame deletion in the N-terminal regulatory domain of BRAF(V600E) causes resistance to the RAF inhibitor PLX4032","publication_year":2011,"publication_date":"2011-04-01","ids":{"openalex":"https://openalex.org/W2312980366","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-419","mag":"2312980366"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2011-lb-419","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-419","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2011-lb-419","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-3","ki-jl-3","medline","norway-2"],"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":"Cancer Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5078118619","display_name":"Poulikos I. Poulikakos","orcid":"https://orcid.org/0000-0001-6071-9963","observed_orcids":["https://orcid.org/0000-0001-6071-9963"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Poulikos I. Poulikakos","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003504569","display_name":"Yogindra Persaud","orcid":"https://orcid.org/0000-0001-8266-9434","observed_orcids":["https://orcid.org/0000-0001-8266-9434","https://orcid.org/0009-0007-5703-8172"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yogindra Persaud","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064474080","display_name":"May Tal Gabay","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"May Tal Gabay","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5004873854","display_name":"Manickam Janakiraman","orcid":"https://orcid.org/0000-0003-4423-6237","observed_orcids":["https://orcid.org/0000-0003-4423-6237"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Manickam Janakiraman","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050393601","display_name":"Eric W. Joseph","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eric W. Joseph","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075174884","display_name":"Christine A. Pratilas","orcid":"https://orcid.org/0000-0002-7116-0605","observed_orcids":["https://orcid.org/0000-0002-7116-0605"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christine A. Pratilas","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083883593","display_name":"Paul B. Chapman","orcid":"https://orcid.org/0000-0003-1618-0811","observed_orcids":["https://orcid.org/0000-0003-1618-0811"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Paul B. Chapman","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060228803","display_name":"Neal X. Rosen","orcid":"https://orcid.org/0000-0002-8307-654X","observed_orcids":["https://orcid.org/0000-0002-8307-654X"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Neal Rosen","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5102710156","display_name":"David B. Solit","orcid":"https://orcid.org/0000-0002-6614-802X","observed_orcids":["https://orcid.org/0000-0002-6614-802X"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David B. Solit","raw_affiliation_strings":["1Memorial Sloan-Kettering Cancer Center, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Memorial Sloan-Kettering Cancer Center, New York, NY","institution_ids":["https://openalex.org/I1334819555"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1334819555"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"71","issue":"8_Supplement","first_page":"LB","last_page":"419"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":0.9994999766349792,"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":0.9994999766349792,"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"}},{"id":"https://openalex.org/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.0,"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/raf-inhibitor-resistance","display_name":"RAF inhibitor resistance","score":0.8740000128746033},{"id":"https://openalex.org/keywords/vemurafenib","display_name":"vemurafenib","score":0.9369999766349792},{"id":"https://openalex.org/keywords/braf-v600e-mutation","display_name":"BRAF V600E mutation","score":0.9480000138282776},{"id":"https://openalex.org/keywords/in-frame-deletion","display_name":"in-frame deletion","score":0.6819999814033508},{"id":"https://openalex.org/keywords/n-terminal-regulatory-domain","display_name":"N-terminal regulatory domain","score":0.953000009059906},{"id":"https://openalex.org/keywords/raf-dimerization","display_name":"RAF dimerization","score":0.921999990940094},{"id":"https://openalex.org/keywords/erk-signaling","display_name":"ERK signaling","score":0.8790000081062317},{"id":"https://openalex.org/keywords/mek-inhibitors","display_name":"MEK inhibitors","score":0.5360000133514404},{"id":"https://openalex.org/keywords/ras-activity","display_name":"Ras activity","score":0.5379999876022339},{"id":"https://openalex.org/keywords/receptor-tyrosine-kinases","display_name":"receptor tyrosine kinase","score":0.7699999809265137},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.31700000166893005}],"concepts":[{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.7580437064170837},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.65040522813797},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6209595203399658},{"id":"https://openalex.org/C2776470698","wikidata":"https://www.wikidata.org/wiki/Q21851559","display_name":"V600E","level":4,"score":0.5535750389099121},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.5188342332839966},{"id":"https://openalex.org/C101544691","wikidata":"https://www.wikidata.org/wiki/Q420511","display_name":"Receptor tyrosine kinase","level":3,"score":0.514144241809845},{"id":"https://openalex.org/C2776131300","wikidata":"https://www.wikidata.org/wiki/Q423111","display_name":"Vemurafenib","level":4,"score":0.49534597992897034},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.4862715005874634},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.47470346093177795},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4507938027381897},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.412314772605896},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.40663230419158936},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3716995120048523},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.2719075083732605},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.16775718331336975},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0715772807598114},{"id":"https://openalex.org/C2994587330","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Metastatic melanoma","level":3,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2011-lb-419","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-419","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2011-lb-419","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-3","ki-jl-3","medline","norway-2"],"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":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.8560000061988831}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.800000011920929}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2033014187","https://openalex.org/W4244963342","https://openalex.org/W4234665826","https://openalex.org/W4213104766","https://openalex.org/W2164959745","https://openalex.org/W1995404972","https://openalex.org/W2129609667","https://openalex.org/W2884023078","https://openalex.org/W1981626262","https://openalex.org/W2011042089"],"abstract_inverted_index":{"Abstract":[0],"Drugs":[1],"that":[2,124,195,327,370],"compete":[3],"with":[4,17,61,107,202,270,314],"ATP":[5],"for":[6,92,430],"binding":[7,42,406],"to":[8,46,69,90,167,188,207,295,326,341,359,392],"RAF":[9,29,44,83,190,291,378,387,399],"selectively":[10],"inhibit":[11,208],"ERK":[12,27,78,163,209,216,338],"signaling":[13,339],"in":[14,34,59,105,129,251,304,311,334,348,357],"tumor":[15,131],"cells":[16,187,212,313,336],"BRAF(V600E)":[18,62,108],"mutation.":[19],"In":[20,38,57,165,254],"BRAF":[21,39,184,360],"wild-type":[22,40],"cells,":[23,41],"these":[24,198,252],"compounds":[25],"induce":[26],"signaling.":[28,79,164,210],"family":[30],"members":[31],"form":[32,267],"dimers":[33],"a":[35,223,255,265,280,346],"RAS-dependent":[36],"manner.":[37],"of":[43,49,82,97,115,126,139,154,156,171,182,197,204,238,244,257,264,268,283,290,318,321,328,332,352,377,384,403,411,421,426],"inhibitors":[45,84],"one":[47],"member":[48],"the":[50,53,74,93,112,130,157,189,205,262,275,298,349,375,381,404,409,422,427],"dimer":[51,71],"transactivates":[52],"other,":[54],"non-bound":[55],"member.":[56],"contrast,":[58],"tumors":[60],"mutation,":[63],"RAS":[64,127,135,235,393,405],"activity":[65,104,128],"is":[66,88,323],"too":[67],"low":[68,316],"support":[70],"formation":[72],"and":[73,100,137,146,279,401],"drug":[75,99,206],"thus":[76],"inhibits":[77],"This":[80],"property":[81],"such":[85],"as":[86,151,218],"PLX4032":[87],"believed":[89],"account":[91],"wide":[94],"therapeutic":[95],"index":[96],"this":[98],"its":[101],"remarkable":[102],"clinical":[103],"patients":[106],"melanomas.":[109],"However,":[110],"despite":[111],"initial":[113],"effectiveness":[114],"PLX4032,":[116,344],"resistance":[117,196,372],"invariably":[118],"develops.":[119],"The":[120,287],"dimerization":[121,320,350],"model":[122],"predicts":[123],"induction":[125,153],"will":[132],"confer":[133,371],"resistance.":[134],"mutation":[136,347,394],"activation":[138],"receptor":[140,239],"tyrosine":[141,240],"kinases":[142,241,247],"(RTK)":[143,397],"including":[144],"PDGFR\u00df":[145],"IGF1R":[147],"have":[148],"been":[149,293],"implicated,":[150],"has":[152,292],"expression":[155,263],"COT":[158],"kinase,":[159],"which":[160,385],"drives":[161],"RAF-independent":[162],"order":[166],"identify":[168],"novel":[169],"mechanisms":[170,369],"RAF-inhibitor":[172],"resistance,":[173],"we":[174,260],"generated":[175],"PLX4032-resistant":[176,211],"cell":[177],"lines":[178],"by":[179,222,306,343,373,380],"prolonged":[180],"exposure":[181],"sensitive":[183],"mutant":[185],"melanoma":[186],"inhibitor":[191],"PLX4032.":[192],"Analysis":[193],"revealed":[194],"clones":[199],"was":[200,220],"associated":[201],"failure":[203],"remained":[213],"dependent":[214],"on":[215],"signaling,":[217],"growth":[219],"inhibited":[221],"MEK":[224,246],"inhibitor,":[225,382],"albeit":[226],"at":[227,302,365],"slightly":[228],"higher":[229],"doses.":[230],"We":[231],"did":[232],"not":[233],"detect":[234],"mutations,":[236,362],"upregulation":[237],"(RTK),":[242],"or":[243,395],"other":[245],"(CRAF,":[248],"COT,":[249],"Mos)":[250],"cells.":[253],"subset":[256],"resistant":[258],"clones,":[259],"identified":[261],"variant":[266],"BRAF(V600E),":[269],"an":[271],"in-frame":[272],"deletion":[273,402],"within":[274,408],"N-terminal":[276,288],"regulatory":[277],"domain":[278,289,351,407],"molecular":[281],"weight":[282],"about":[284],"61KD":[285],"(p61BRAF(V600E)).":[286],"shown":[294],"negatively":[296],"regulate":[297],"C-terminal":[299],"catalytic":[300],"domain,":[301],"least":[303,366],"part,":[305],"preventing":[307],"dimerization.":[308],"When":[309],"expressed":[310],"293H":[312,335],"intrincically":[315],"levels":[317],"RAS.GTP,":[319],"p61BRAF(V600E)":[322,333,353],"elevated":[324],"compared":[325],"full-length":[329],"BRAF(V600E).":[330],"Expression":[331],"rendered":[337],"insensitive":[340],"inhibition":[342,376],"whereas":[345],"restored":[354],"sensitivity.":[355],"Thus,":[356],"addition":[358],"gatekeeper":[361],"there":[363],"are":[364],"three":[367],"potential":[368],"blunting":[374],"kinase":[379],"all":[383],"promote":[386],"dimerization:":[388],"increased":[389],"RAS.GTP":[390],"due":[391],"upstream":[396],"activation,":[398],"overexpression":[400],"N-terminus":[410],"RAF.":[412],"Citation":[413],"Format:":[414],"{Authors}.":[415],"{Abstract":[416],"title}":[417],"[abstract].":[418],"In:":[419],"Proceedings":[420],"102nd":[423],"Annual":[424],"Meeting":[425],"American":[428],"Association":[429],"Cancer":[431,441],"Research;":[432],"2011":[433],"Apr":[434],"2-6;":[435],"Orlando,":[436],"FL.":[437],"Philadelphia":[438],"(PA):":[439],"AACR;":[440],"Res":[442],"2011;71(8":[443],"Suppl):Abstract":[444],"nr":[445],"LB-419.":[446],"doi:10.1158/1538-7445.AM2011-LB-419":[447]},"counts_by_year":[],"updated_date":"2026-09-24T07:57:37.273135","created_date":"2025-10-10T00:00:00"}