{"id":"https://openalex.org/W2314735100","doi":"https://doi.org/10.1111/j.1755-148x.2012.00991.x","title":"Active surrender","display_name":"Active surrender","publication_year":2012,"publication_date":"2012-02-25","ids":{"openalex":"https://openalex.org/W2314735100","doi":"https://doi.org/10.1111/j.1755-148x.2012.00991.x","mag":"2314735100","pmid":"https://pubmed.ncbi.nlm.nih.gov/22629566"},"language":"en","primary_location":{"id":"doi:10.1111/j.1755-148x.2012.00991.x","doi":"https://doi.org/10.1111/j.1755-148x.2012.00991.x","is_oa":true,"landing_page_url":"https://doi.org/10.1111/j.1755-148x.2012.00991.x","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1755-148X.2012.00991.x","source":{"id":"https://openalex.org/S179442820","display_name":"Pigment Cell & Melanoma Research","issn_l":"1755-1471","issn":["1755-1471","1755-148X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Pigment Cell & Melanoma Research","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1755-148X.2012.00991.x","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5035793503","display_name":"Eric Andrew Collisson","orcid":"https://orcid.org/0000-0001-8037-9388","observed_orcids":["https://orcid.org/0000-0001-8037-9388","https://orcid.org/0000-0002-2829-355X"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Eric A. Collisson","raw_affiliation_strings":["eric.collisson@ucsf.edu","e-mail: [email protected]"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"eric.collisson@ucsf.edu","institution_ids":[]},{"raw_affiliation_string":"e-mail: [email protected]","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5035793503"],"corresponding_institution_ids":[],"apc_list":{"value":5000,"currency":"USD","value_usd":5000},"apc_paid":null,"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.16541376,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"25","issue":"3","first_page":"292","last_page":"293"},"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.0027000000700354576,"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/T10392","display_name":"Cutaneous Melanoma Detection and Management","score":0.0003000000142492354,"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/metastatic-melanoma","display_name":"metastatic melanoma","score":0.9120000004768372},{"id":"https://openalex.org/keywords/braf-mutation","display_name":"BRAF mutation","score":0.7409999966621399},{"id":"https://openalex.org/keywords/raf-inhibitor-resistance","display_name":"RAF inhibitor resistance","score":0.8330000042915344},{"id":"https://openalex.org/keywords/wnt-signaling","display_name":"Wnt signaling","score":0.5870000123977661},{"id":"https://openalex.org/keywords/mapk-signaling","display_name":"MAPK signaling","score":0.4860000014305115},{"id":"https://openalex.org/keywords/targeted-therapy-response","display_name":"targeted therapy response","score":0.4399999976158142},{"id":"https://openalex.org/keywords/predictive-biomarkers","display_name":"predictive biomarkers","score":0.5730000138282776},{"id":"https://openalex.org/keywords/acquired-resistance-mechanisms","display_name":"acquired resistance mechanisms","score":0.42399999499320984},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.4259999990463257},{"id":"https://openalex.org/keywords/braf-v600e-mutation","display_name":"BRAF V600E mutation","score":0.47200000286102295},{"id":"https://openalex.org/keywords/mapk-inhibitor-resistance","display_name":"MAPK inhibitor resistance","score":0.3050000071525574}],"concepts":[{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.740478515625},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6203855872154236},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.5483617186546326},{"id":"https://openalex.org/C2776131300","wikidata":"https://www.wikidata.org/wiki/Q423111","display_name":"Vemurafenib","level":4,"score":0.5238677859306335},{"id":"https://openalex.org/C2994294914","wikidata":"https://www.wikidata.org/wiki/Q1645075","display_name":"Acquired resistance","level":3,"score":0.45258885622024536},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.44396883249282837},{"id":"https://openalex.org/C114851261","wikidata":"https://www.wikidata.org/wiki/Q12147416","display_name":"Drug resistance","level":2,"score":0.42320170998573303},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.34654802083969116},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.2889571189880371},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2506358027458191},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.23706984519958496},{"id":"https://openalex.org/C2994587330","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Metastatic melanoma","level":3,"score":0.17126819491386414},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.1656126081943512}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D002471","descriptor_name":"Cell Transformation, Neoplastic","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D002471","descriptor_name":"Cell Transformation, Neoplastic","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008495","descriptor_name":"Medical Oncology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false},{"descriptor_ui":"D008495","descriptor_name":"Medical Oncology","qualifier_ui":"Q000639","qualifier_name":"trends","is_major_topic":true},{"descriptor_ui":"D008545","descriptor_name":"Melanoma","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D008545","descriptor_name":"Melanoma","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D008545","descriptor_name":"Melanoma","qualifier_ui":"Q000628","qualifier_name":"therapy","is_major_topic":true},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D012878","descriptor_name":"Skin Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D012878","descriptor_name":"Skin Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D012878","descriptor_name":"Skin Neoplasms","qualifier_ui":"Q000628","qualifier_name":"therapy","is_major_topic":true},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D016896","descriptor_name":"Treatment Outcome","qualifier_ui":null,"qualifier_name":null,"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":false},{"descriptor_ui":"D048490","descriptor_name":"raf Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048490","descriptor_name":"raf Kinases","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D058990","descriptor_name":"Molecular Targeted Therapy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1111/j.1755-148x.2012.00991.x","doi":"https://doi.org/10.1111/j.1755-148x.2012.00991.x","is_oa":true,"landing_page_url":"https://doi.org/10.1111/j.1755-148x.2012.00991.x","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1755-148X.2012.00991.x","source":{"id":"https://openalex.org/S179442820","display_name":"Pigment Cell & Melanoma Research","issn_l":"1755-1471","issn":["1755-1471","1755-148X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Pigment Cell & Melanoma Research","raw_type":"journal-article"},{"id":"pmid:22629566","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/22629566","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":"Pigment cell & melanoma research","raw_type":"News"}],"best_oa_location":{"id":"doi:10.1111/j.1755-148x.2012.00991.x","doi":"https://doi.org/10.1111/j.1755-148x.2012.00991.x","is_oa":true,"landing_page_url":"https://doi.org/10.1111/j.1755-148x.2012.00991.x","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1755-148X.2012.00991.x","source":{"id":"https://openalex.org/S179442820","display_name":"Pigment Cell & Melanoma Research","issn_l":"1755-1471","issn":["1755-1471","1755-148X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Pigment Cell & Melanoma Research","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9537000060081482}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2314735100.pdf","grobid_xml":"https://content.openalex.org/works/W2314735100.grobid-xml"},"referenced_works_count":4,"referenced_works":["https://openalex.org/W1606580446","https://openalex.org/W2050839565","https://openalex.org/W2112140640","https://openalex.org/W2128542677"],"related_works":["https://openalex.org/W7163522211","https://openalex.org/W2009228205","https://openalex.org/W1996765884","https://openalex.org/W1964896102","https://openalex.org/W2001193463","https://openalex.org/W2033240778","https://openalex.org/W2105660237","https://openalex.org/W2037661105","https://openalex.org/W2069218810","https://openalex.org/W1527410143"],"abstract_inverted_index":{"In":[0,101],"the":[1,24,75,87,104,156,175,187,230,262,328,333,339,352,372,405,448,452,465,481,495,507,552,562,569,578,606,621,654,681,713,754,796,826,829,843,871,875,880,898],"not":[2,199,442],"so":[3,108,112,439,746],"distant":[4],"past,":[5],"clinical":[6],"management":[7],"of":[8,43,133,143,150,186,232,271,277,316,330,336,354,371,379,404,419,454,485,497,589,602,608,620,669,676,728,756,822,831,845,900,905],"melanoma":[9,28,120,363,459,486,538,659,720,791,824],"beyond":[10,903],"surgical":[11],"excision":[12],"was":[13,29,611],"largely":[14,800],"futile.":[15],"As":[16,586],"with":[17,36,327,649,787,855],"many":[18,102],"other":[19,317],"diseases":[20],"in":[21,41,74,111,131,155,174,181,205,221,254,290,314,320,360,393,408,412,456,464,480,512,557,582,595,615,632,692,710,730,790,805,809,818,852,857,874,882],"medical":[22],"oncology,":[23],"treatment":[25,195,297],"for":[26,196,433],"metastatic":[27],"centered":[30],"upon":[31],"chemotherapies":[32],"or":[33,312,426],"immunologic":[34],"modulations":[35],"little":[37,57,113],"to":[38,60,124,169,192,217,246,261,309,324,357,381,444,462,521,618,663,694,732,744,750,765,780,802,836,866,895],"recommend":[39],"them":[40],"terms":[42,292],"objective":[44],"response":[45,226,311,380,685,693,731],"rates,":[46],"and":[47,90,138,224,293,365,483,499,509,545,574,592,629,640,679],"substantial":[48,275],"toxicity.":[49],"When":[50],"rare":[51],"responses":[52,260,356,617,835],"were":[53,686],"seen,":[54],"we":[55,400,470,769,892],"had":[56],"insight":[58],"as":[59,177,375,580],"why":[61,247],"a":[62,237,367,376,390,420,531,583,587,612,672,700,718,761,819,862,867],"given":[63,719],"patient":[64],"would":[65,69,689,792],"respond":[66,123,865],"whereas":[67,739],"another":[68,778],"not.":[70],"Much":[71],"has":[72,106,243,347],"changed":[73],"last":[76],"5\u201310":[77],"years.":[78],"Melanoma":[79],"genomes":[80],"have":[81,94,190,213,257],"been":[82,95,244],"sequenced,":[83],"novel":[84],"oncogenes":[85],"driving":[86],"disease":[88],"discovered,":[89],"highly":[91],"effective":[92,194],"therapies":[93,127,902],"approved":[96],"(Chapman":[97,207],"et":[98,208,344,488,515],"al.,":[99,209,489],"2011).":[100,210],"ways":[103],"field":[105],"moved":[107],"far":[109],"forward":[110],"time":[114],"that":[115,249,446,475,551,600,627,641,657,680,688,716,742,768],"fundamental":[116],"questions":[117],"about":[118,269],"how":[119,500,861],"cells":[121,364,460,559],"actually":[122],"these":[125,558,590],"new":[126,134,349],"risk":[128],"being":[129],"couched":[130],"favor":[132,315],"drug":[135,881],"combination":[136],"regimens":[137],"ever":[139],"more":[140,397],"complex":[141],"mechanisms":[142,287],"acquired":[144,215,233],"RAF":[145,188,284,303,382,455,555,664,733,751],"inhibitor":[146,285,304],"resistance.":[147],"About":[148],"half":[149,270],"melanomas":[151,705,741],"harbor":[152,250],"activating":[153,203,784],"mutations":[154,167,204,253,709],"BRAF":[157,206,255,361,544],"gene,":[158],"rendering":[159],"its":[160,806],"protein":[161],"kinase":[162],"product":[163],"constitutively":[164,553],"active.":[165],"These":[166,696,758],"appear":[168],"be":[170,193,288,306,325,737,748,803,893],"an":[171,413,637,889],"early":[172],"event":[173,614],"disease,":[176],"they":[178,430,598],"are":[179,424,431,436],"present":[180],"most":[182],"nevi.":[183],"Potent":[184],"inhibitors":[185],"kinases":[189,523],"proven":[191],"many,":[197],"but":[198],"all":[200],"patients":[201,248,273,322,337],"harboring":[202,706],"Numerous":[211],"groups":[212],"investigated":[214],"resistance":[216,234,286],"such":[218,272,888],"agents":[219,856],"(reviewed":[220],"Mcmahon,":[222],"2011),":[223],"because":[225,403,429,469,795,859],"is":[227,236,298,389,441,478,492,494,799,885],"often":[228],"short-lived,":[229],"identification":[231],"pathways":[235,388,411,423,511],"high":[238],"priority.":[239],"Relatively":[240],"less":[241],"attention":[242],"paid":[245],"identical":[251,263,708],"drug-sensitizing":[252],"will":[256,736,747,864,891],"markedly":[258],"different":[259],"targeted":[264],"therapy.":[265,757,782],"Why":[266],"do":[267,745],"only":[268,886],"enjoy":[274],"shrinkage":[276],"their":[278,596,650],"disease?":[279],"Can":[280],"primary":[281,355,377,833],"(de":[282],"novo)":[283],"understood":[289],"molecular":[291],"therefore":[294],"predicted":[295,323],"before":[296],"administered?":[299],"If":[300],"so,":[301],"could":[302],"therapy":[305,868],"either":[307],"modified":[308],"maximize":[310],"held":[313],"therapies,":[318],"specifically":[319],"those":[321,687,740],"resistant,":[326],"goal":[329],"effectively":[331],"treating":[332],"greatest":[334],"proportion":[335],"from":[338,342,472,753],"onset?":[340],"Work":[341],"Biechele":[343,514],"al.":[345,516],"(2012)":[346,517],"shed":[348],"light":[350],"on":[351,568,645],"issue":[353],"Raf":[358,368,510,573],"inhibition":[359,619,665,752],"mutant":[362],"implicates":[366],"inhibitor-induced":[369],"modulation":[370],"Wnt":[373,476,508,528,563,603,677,722,785,797],"pathway":[374,450,556,564,571,774,798,837],"determinant":[378],"inhibition.":[383,838],"Cross":[384],"talk":[385],"between":[386,506,704],"signaling":[387,477,529,723,786],"common":[391,398],"occurrence":[392],"cancer":[394,766,863],"cells,":[395],"undoubtedly":[396],"than":[399],"currently":[401],"appreciate":[402],"inherent":[406],"difficulty":[407],"examining":[409],"parallel":[410],"unbiased":[414],"manner":[415],"after":[416],"experimental":[417],"manipulation":[418],"system.":[421],"Cancer":[422],"mutated":[425],"otherwise":[427,707],"deregulated":[428],"important":[432,479,702],"growth.":[434],"Cells":[435],"dynamic":[437],"systems,":[438],"it":[440,501,735],"surprising":[443,493],"learn":[445],"inhibiting":[447,726,777],"RAF/MEK/ERK":[449,570],"at":[451,565,605],"level":[453,607],"BRAFV600E":[457,535],"expressing":[458],"leads":[461],"alteration":[463],"Wnt/beta":[466],"catenin":[467,533],"pathway,":[468],"know":[471],"prior":[473,593],"work":[474,594,714,827,840],"genesis":[482],"maintenance":[484],"(Delmas":[487],"2007).":[490],"What":[491],"directionality":[496],"change":[498],"occurs":[502],"(Figure":[503],"1).":[504],"Crosstalk":[505],"melanoma.":[513],"use":[518],"siRNA":[519],"screening":[520],"identify":[522],"whose":[524],"depletion":[525],"might":[526],"alter":[527],"using":[530],"beta":[532,609,646],"reporter-modified":[534],"A375":[536,633],"human":[537],"cell":[539,634,660,877],"line.":[540],"Surprisingly,":[541],"siRNAs":[542],"against":[543],"MAPK1":[546],"activated":[547,577],"this":[548,642,684,810,813],"reporter,":[549],"indicating":[550],"active":[554],"tonically":[560],"inhibited":[561],"baseline.":[566],"Drugs":[567],"(both":[572],"MEK":[575],"inhibitors)":[576],"reporter":[579,651],"well,":[581],"dose-dependent":[584],"manner.":[585],"result":[588],"observations":[591],"laboratory,":[597],"concluded":[599],"activation":[601],"signaling,":[604,678],"catenin,":[610,647],"key":[613,673],"acute":[616],"Raf/MAPK":[622],"pathway.":[623],"The":[624,839],"authors":[625,655],"demonstrate":[626],"WNT3A":[628],"PLX4720":[630],"synergize":[631],"killing":[635],"though":[636],"apoptosis":[638,691],"mechanism,":[639],"effect":[643],"depends":[644],"consistent":[648],"screens.":[652],"Interestingly,":[653],"find":[656],"some":[658],"lines":[661,682],"responded":[662],"by":[666,725,879],"decreasing":[667],"levels":[668,727],"AXIN1":[670],"protein,":[671],"negative":[674],"regulator":[675],"demonstrating":[683],"undergo":[690],"PLX4720.":[695],"results":[697],"together":[698],"suggest":[699,760],"potentially":[701],"distinction":[703],"BRAF.":[711,906],"Specifically,":[712],"implies":[715],"if":[717],"activates":[721],"(likely":[724],"AXIN)":[729],"inhibition,":[734],"sensitive,":[738],"fail":[743],"resistant":[749],"start":[755],"findings":[759],"somewhat":[762],"paradoxical":[763],"approach":[764,814],"treatment:":[767],"should":[770],"stimulate":[771],"one":[772],"oncogenic":[773,804],"(Wnt)":[775],"while":[776],"(RAF/MEK/EFRK)":[779],"optimize":[781],"Intentionally":[783],"therapeutic":[788],"intent":[789],"raise":[793],"controversy,":[794],"thought":[801],"own":[807],"right":[808],"disease.":[811],"While":[812],"requires":[815,869],"further":[816,841,896],"examination":[817],"wider":[820],"array":[821],"preclinical":[823],"models,":[825],"underscores":[828,842],"importance":[830,844],"understanding":[832,860,890],"cellular":[834],"obtaining":[846],"\u2018on":[847],"treatment\u2019":[848],"biopsies":[849],"per":[850],"protocol":[851],"ongoing":[853],"trials":[854],"melanoma,":[858],"knowing":[870],"earliest":[872],"changes":[873],"tumor":[876],"induced":[878],"question.":[883],"It":[884],"through":[887],"able":[894],"personalize":[897],"application":[899],"specific":[901],"genotyping":[904]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}