{"id":"https://openalex.org/W2094638685","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-228","title":"Abstract LB-228: Resistance to BRAF inhibition in BRAF V600E colorectal cancer is associated with PI3K/AKT activation and hypermethylation","display_name":"Abstract LB-228: Resistance to BRAF inhibition in BRAF V600E colorectal cancer is associated with PI3K/AKT activation and hypermethylation","publication_year":2011,"publication_date":"2011-04-01","ids":{"openalex":"https://openalex.org/W2094638685","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-228","mag":"2094638685"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2011-lb-228","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-228","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2011-lb-228","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":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","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":"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/A5112904848","display_name":"Muling Mao","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Muling Mao","raw_affiliation_strings":["1MDACC, Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1MDACC, Houston, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5017611068","display_name":"Lawrence Tsao","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lawrence Tsao","raw_affiliation_strings":["1MDACC, Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1MDACC, Houston, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022820783","display_name":"Farshid Dayyani","orcid":"https://orcid.org/0000-0002-4970-5189","observed_orcids":["https://orcid.org/0000-0002-4970-5189"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Farshid Dayyani","raw_affiliation_strings":["1MDACC, Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1MDACC, Houston, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044747566","display_name":"Vashisht Gopal Yennu Nanda","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Vashisht Gopal Yennu Nanda","raw_affiliation_strings":["1MDACC, Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1MDACC, Houston, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005221518","display_name":"Gordon Brent Mills","orcid":"https://orcid.org/0000-0002-0144-9614","observed_orcids":["https://orcid.org/0000-0002-0144-9614"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gordon Mills","raw_affiliation_strings":["1MDACC, Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1MDACC, Houston, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069230508","display_name":"Gideon E. Bollag","orcid":"https://orcid.org/0000-0002-1824-6194","observed_orcids":["https://orcid.org/0000-0002-1824-6194"]},"institutions":[{"id":"https://openalex.org/I4391768022","display_name":"Plexxikon (United States)","ror":"https://ror.org/00qk1xk35","country_code":"US","type":"company","lineage":["https://openalex.org/I4210104626","https://openalex.org/I4391768022"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gideon Bollag","raw_affiliation_strings":["2Plexxikon Inc., Berkeley, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Plexxikon Inc., Berkeley, CA","institution_ids":["https://openalex.org/I4391768022"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5048327749","display_name":"Michael A. Davies","orcid":"https://orcid.org/0000-0002-0977-0912","observed_orcids":["https://orcid.org/0000-0002-0977-0912"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michael Davies","raw_affiliation_strings":["1MDACC, Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1MDACC, Houston, TX","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111690153","display_name":"Gary E. Gallick","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gary Gallick","raw_affiliation_strings":["1MDACC, Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1MDACC, Houston, TX","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5006348751","display_name":"Scott Kopetz","orcid":"https://orcid.org/0000-0001-9647-3416","observed_orcids":["https://orcid.org/0000-0001-9647-3416"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Scott Kopetz","raw_affiliation_strings":["1MDACC, Houston, TX"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1MDACC, Houston, TX","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"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":"228"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.8705999851226807,"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"}},"topics":[{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.8705999851226807,"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"}},{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":0.10440000146627426,"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.0026000000070780516,"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/braf-v600e-mutation","display_name":"BRAF V600E mutation","score":0.9390000104904175},{"id":"https://openalex.org/keywords/colorectal-cancer","display_name":"colorectal cancer","score":0.9330000281333923},{"id":"https://openalex.org/keywords/braf-inhibitor-resistance","display_name":"BRAF inhibitor resistance","score":0.8510000109672546},{"id":"https://openalex.org/keywords/plx4720","display_name":"PLX4720","score":0.8740000128746033},{"id":"https://openalex.org/keywords/pi3k-akt-signaling","display_name":"PI3K/Akt signaling","score":0.9039999842643738},{"id":"https://openalex.org/keywords/pten","display_name":"PTEN","score":0.8140000104904175},{"id":"https://openalex.org/keywords/dna-methylation","display_name":"DNA methylation","score":0.6819999814033508},{"id":"https://openalex.org/keywords/gsk-3beta","display_name":"GSK3\u03b2","score":0.8169999718666077},{"id":"https://openalex.org/keywords/mek-erk-signaling","display_name":"MEK/ERK signaling","score":0.8389999866485596},{"id":"https://openalex.org/keywords/pi3k-inhibitors","display_name":"PI3K inhibitors","score":0.8600000143051147},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.8759999871253967},{"id":"https://openalex.org/keywords/melanoma","display_name":"melanoma","score":0.4050000011920929},{"id":"https://openalex.org/keywords/g1-cell-cycle-arrest","display_name":"G1 cell cycle arrest","score":0.6499999761581421}],"concepts":[{"id":"https://openalex.org/C2777609662","wikidata":"https://www.wikidata.org/wiki/Q416356","display_name":"PTEN","level":4,"score":0.8248922824859619},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.7619178891181946},{"id":"https://openalex.org/C2776470698","wikidata":"https://www.wikidata.org/wiki/Q21851559","display_name":"V600E","level":4,"score":0.7185060381889343},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.6880826950073242},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.6053546071052551},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.560804009437561},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.5451636910438538},{"id":"https://openalex.org/C2779277951","wikidata":"https://www.wikidata.org/wiki/Q5255196","display_name":"Demethylating agent","level":5,"score":0.4406697750091553},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4271458387374878},{"id":"https://openalex.org/C2781249067","wikidata":"https://www.wikidata.org/wiki/Q17142288","display_name":"MEK inhibitor","level":4,"score":0.4190804362297058},{"id":"https://openalex.org/C119056186","wikidata":"https://www.wikidata.org/wiki/Q1431332","display_name":"Gene silencing","level":3,"score":0.41526076197624207},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4090126156806946},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.36078768968582153},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.34243646264076233},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.28961098194122314},{"id":"https://openalex.org/C190727270","wikidata":"https://www.wikidata.org/wiki/Q874745","display_name":"DNA methylation","level":4,"score":0.2750420570373535},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.20966145396232605},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.2079581618309021},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.08483952283859253},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.06891593337059021},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.06080907583236694},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.049088120460510254}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2011-lb-228","doi":"https://doi.org/10.1158/1538-7445.am2011-lb-228","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2011-lb-228","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":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","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":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9537000060081482}],"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/W2141172646","https://openalex.org/W2047259867","https://openalex.org/W2149528253","https://openalex.org/W2014881369","https://openalex.org/W2064492675","https://openalex.org/W2606849884","https://openalex.org/W2022955746","https://openalex.org/W4393090939","https://openalex.org/W2110682589","https://openalex.org/W2493930640"],"abstract_inverted_index":{"Abstract":[0],"BRAF":[1,21,32,49,56,60,70,78,121,156,178,194,250,261],"V600E":[2,50,57,71,79,122,179,195,251],"mutation":[3],"has":[4,34,62,189],"been":[5,63,190],"detected":[6],"in":[7,17,38,48,98,147,174,228,246],"approximately":[8],"8%":[9],"of":[10,20,31,55,91,112,128,136,144,161,177,266,275,294,299],"metastatic":[11],"colorectal":[12,103,196,255],"cancers":[13,197],"(CRC)":[14],"and":[15,22,93,114,130,169,184,223,236],"results":[16],"constitutive":[18],"activation":[19,97],"the":[23,133,155,202,219,295,300],"downstream":[24,95],"MEK-ERK1/2":[25],"pathway.":[26],"PLX4032,":[27,113],"a":[28,175,264],"selective":[29],"inhibitor":[30],"V600E,":[33],"shown":[35,192],"meaningful":[36],"activity":[37,47],"melanoma":[39,80],"(greater":[40],"than":[41],"70%":[42],"response)":[43],"but":[44,233],"only":[45],"modest":[46],"CRC":[51,58,72,99],"(5%).":[52],"The":[53],"resistance":[54],"to":[59,77,108,138,154,259,272],"inhibitors":[61,282],"poorly":[64],"understood.":[65],"To":[66],"explore":[67],"these":[68],"differences,":[69],"cell":[73,81,100,229,252],"lines":[74,82,230],"were":[75,118],"compared":[76],"by":[83],"reverse-phase":[84],"proteomic":[85],"array,":[86],"which":[87,146,208],"demonstrated":[88],"higher":[89],"levels":[90],"phospho-AKT":[92,129],"associated":[94,200,210,238],"pathway":[96,281],"lines.":[101,253],"Both":[102],"cancer":[104,256],"cells":[105,153,180,257],"inherently":[106],"resistant":[107,115],"PLX4720,":[109],"an":[110],"analog":[111],"subclones":[116],"that":[117,193],"derived":[119],"from":[120],"positive":[123],"cells,":[124],"showed":[125],"increased":[126,267],"expression":[127],"phospho-GSK3\u03b2,":[131],"despite":[132],"sustained":[134],"ability":[135],"PLX4720":[137,162],"effectively":[139],"inhibit":[140],"MEK":[141],"signaling.":[142],"Silencing":[143],"PTEN,":[145,235],"turn":[148],"induced":[149],"AKT":[150],"activation,":[151],"desensitized":[152],"inhibitor.":[157],"Furthermore,":[158],"combined":[159],"treatment":[160,217],"with":[163,201,211,218,231,239,279],"two":[164],"different":[165],"PI3K":[166],"inhibitors,":[167],"LY294002":[168],"GDC-0941,":[170],"synergistically":[171],"inhibited":[172],"growth":[173],"panel":[176],"through":[181,263],"both":[182],"apoptosis":[183],"G1":[185],"phase":[186],"arrest.":[187],"It":[188],"previously":[191],"are":[198],"commonly":[199],"CpG":[203],"island":[204],"methylation":[205],"phenotype":[206],"(CIMP),":[207],"is":[209],"epigenetically":[212],"diminished":[213],"PTEN":[214,240,249],"expression.":[215],"Combination":[216],"demethylating":[220,284],"agent":[221],"azacitadine":[222],"PLX4032":[224],"was":[225,237,243],"also":[226],"synergistic":[227],"intact":[232],"suppressed":[234],"re-expression.":[241],"This":[242],"not":[244],"seen":[245],"non-CIMP":[247],"or":[248,283],"Thus,":[254],"appear":[258],"escape":[260],"targeting":[262],"mechanism":[265],"PI3K/AKT":[268,280],"activity,":[269],"providing":[270],"evidence":[271],"support":[273],"investigation":[274],"new":[276],"combination":[277],"therapies":[278],"agents.":[285],"Citation":[286],"Format:":[287],"{Authors}.":[288],"{Abstract":[289],"title}":[290],"[abstract].":[291],"In:":[292],"Proceedings":[293],"102nd":[296],"Annual":[297],"Meeting":[298],"American":[301],"Association":[302],"for":[303],"Cancer":[304,314],"Research;":[305],"2011":[306],"Apr":[307],"2-6;":[308],"Orlando,":[309],"FL.":[310],"Philadelphia":[311],"(PA):":[312],"AACR;":[313],"Res":[315],"2011;71(8":[316],"Suppl):Abstract":[317],"nr":[318],"LB-228.":[319],"doi:10.1158/1538-7445.AM2011-LB-228":[320]},"counts_by_year":[{"year":2018,"cited_by_count":1}],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2016-06-24T00:00:00"}