{"id":"https://openalex.org/W2086409166","doi":"https://doi.org/10.1002/cncr.24234","title":"Combination targeted therapy in advanced renal cell carcinoma","display_name":"Combination targeted therapy in advanced renal cell carcinoma","publication_year":2009,"publication_date":"2009-04-28","ids":{"openalex":"https://openalex.org/W2086409166","doi":"https://doi.org/10.1002/cncr.24234","mag":"2086409166","pmid":"https://pubmed.ncbi.nlm.nih.gov/19402058"},"language":"en","primary_location":{"id":"doi:10.1002/cncr.24234","doi":"https://doi.org/10.1002/cncr.24234","is_oa":true,"landing_page_url":"https://doi.org/10.1002/cncr.24234","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cncr.24234","source":{"id":"https://openalex.org/S126033908","display_name":"Cancer","issn_l":"0008-543X","issn":["0008-543X","1045-7410","1097-0142"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/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":"Cancer","raw_type":"journal-article"},"volume":null,"type":"review","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cncr.24234","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5075566772","display_name":"Jeffrey Alan Sosman","orcid":"https://orcid.org/0000-0002-0650-9698","observed_orcids":["https://orcid.org/0000-0002-0650-9698"]},"institutions":[{"id":"https://openalex.org/I4390039299","display_name":"Vanderbilt-Ingram Cancer Center","ror":"https://ror.org/02rjj2m04","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210162197","https://openalex.org/I4390039299","https://openalex.org/I901861585"]},{"id":"https://openalex.org/I901861585","display_name":"Vanderbilt University Medical Center","ror":"https://ror.org/05dq2gs74","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210162197","https://openalex.org/I901861585"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jeffrey Sosman","raw_affiliation_strings":["Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 777 Preston Building, Nashville, TN 37232-6307, USA. jeff.sosman@vanderbilt.edu","Division of Hematology/Oncology Vanderbilt University Medical Center  Nashville Tennessee"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 777 Preston Building, Nashville, TN 37232-6307, USA. jeff.sosman@vanderbilt.edu","institution_ids":["https://openalex.org/I4390039299","https://openalex.org/I901861585"]},{"raw_affiliation_string":"Division of Hematology/Oncology Vanderbilt University Medical Center  Nashville Tennessee","institution_ids":["https://openalex.org/I901861585"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5049243227","display_name":"Igor J. Puzanov","orcid":"https://orcid.org/0000-0002-9803-3497","observed_orcids":["https://orcid.org/0000-0002-9803-3497"]},"institutions":[{"id":"https://openalex.org/I901861585","display_name":"Vanderbilt University Medical Center","ror":"https://ror.org/05dq2gs74","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210162197","https://openalex.org/I901861585"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Igor Puzanov","raw_affiliation_strings":["Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee","institution_ids":["https://openalex.org/I901861585"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5075566772"],"corresponding_institution_ids":["https://openalex.org/I4390039299","https://openalex.org/I901861585"],"apc_list":{"value":4790,"currency":"USD","value_usd":4790},"apc_paid":null,"fwci":1.2896,"has_fulltext":true,"cited_by_count":46,"citation_normalized_percentile":{"value":0.78283351,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"115","issue":"S10","first_page":"2368","last_page":"2375"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10449","display_name":"Renal cell carcinoma treatment","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/T10449","display_name":"Renal cell carcinoma treatment","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/T10422","display_name":"Angiogenesis and VEGF in Cancer","score":0.00019999999494757503,"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/T10458","display_name":"Bladder and Urothelial Cancer Treatments","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"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/advanced-renal-cell-carcinoma","display_name":"advanced renal cell carcinoma","score":0.9919999837875366},{"id":"https://openalex.org/keywords/combination-targeted-therapy","display_name":"combination targeted therapy","score":0.9300000071525574},{"id":"https://openalex.org/keywords/mtor-inhibitors","display_name":"mTOR inhibitors","score":0.7979999780654907},{"id":"https://openalex.org/keywords/sorafenib","display_name":"sorafenib","score":0.796999990940094},{"id":"https://openalex.org/keywords/bevacizumab","display_name":"bevacizumab","score":0.9919999837875366},{"id":"https://openalex.org/keywords/temsirolimus","display_name":"temsirolimus","score":0.9459999799728394},{"id":"https://openalex.org/keywords/sunitinib","display_name":"sunitinib","score":1.0},{"id":"https://openalex.org/keywords/drug-toxicity","display_name":"drug toxicity","score":0.6269999742507935},{"id":"https://openalex.org/keywords/hand-foot-syndrome","display_name":"hand-foot syndrome","score":0.9279999732971191},{"id":"https://openalex.org/keywords/proteinuria","display_name":"proteinuria","score":0.7229999899864197},{"id":"https://openalex.org/keywords/hypertension","display_name":"hypertension","score":0.7089999914169312},{"id":"https://openalex.org/keywords/microangiopathic-hemolytic-anemia","display_name":"microangiopathic hemolytic anemia","score":0.9470000267028809},{"id":"https://openalex.org/keywords/hypoxia-inducible-factor","display_name":"hypoxia-inducible factor","score":0.8700000047683716}],"concepts":[{"id":"https://openalex.org/C2776820818","wikidata":"https://www.wikidata.org/wiki/Q7699074","display_name":"Temsirolimus","level":5,"score":0.9227603673934937},{"id":"https://openalex.org/C2779490328","wikidata":"https://www.wikidata.org/wiki/Q417542","display_name":"Sunitinib","level":3,"score":0.9007875323295593},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8565967082977295},{"id":"https://openalex.org/C2778695046","wikidata":"https://www.wikidata.org/wiki/Q421136","display_name":"Sorafenib","level":3,"score":0.745988130569458},{"id":"https://openalex.org/C2777802072","wikidata":"https://www.wikidata.org/wiki/Q413299","display_name":"Bevacizumab","level":3,"score":0.697815477848053},{"id":"https://openalex.org/C2777025900","wikidata":"https://www.wikidata.org/wiki/Q29725","display_name":"Vascular endothelial growth factor","level":3,"score":0.5768441557884216},{"id":"https://openalex.org/C2777472916","wikidata":"https://www.wikidata.org/wiki/Q1164529","display_name":"Renal cell carcinoma","level":2,"score":0.5121796131134033},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.48892393708229065},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.4599856734275818},{"id":"https://openalex.org/C2779699572","wikidata":"https://www.wikidata.org/wiki/Q421052","display_name":"Everolimus","level":2,"score":0.455780953168869},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4344692826271057},{"id":"https://openalex.org/C2776999253","wikidata":"https://www.wikidata.org/wiki/Q1304270","display_name":"Combination therapy","level":2,"score":0.42292308807373047},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3884415328502655},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.31122034788131714},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.1410626769065857},{"id":"https://openalex.org/C2778019345","wikidata":"https://www.wikidata.org/wiki/Q1148337","display_name":"Hepatocellular carcinoma","level":2,"score":0.10509705543518066},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.10073038935661316},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0887850821018219},{"id":"https://openalex.org/C167734588","wikidata":"https://www.wikidata.org/wiki/Q4356503","display_name":"VEGF receptors","level":2,"score":0.07049787044525146},{"id":"https://openalex.org/C183713625","wikidata":"https://www.wikidata.org/wiki/Q5282002","display_name":"Discovery and development of mTOR inhibitors","level":4,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000971","descriptor_name":"Antineoplastic Combined Chemotherapy Protocols","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D002986","descriptor_name":"Clinical Trials as Topic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D011494","descriptor_name":"Protein Kinases","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D016503","descriptor_name":"Drug Delivery Systems","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020533","descriptor_name":"Angiogenesis Inhibitors","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D058570","descriptor_name":"TOR Serine-Threonine Kinases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1002/cncr.24234","doi":"https://doi.org/10.1002/cncr.24234","is_oa":true,"landing_page_url":"https://doi.org/10.1002/cncr.24234","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cncr.24234","source":{"id":"https://openalex.org/S126033908","display_name":"Cancer","issn_l":"0008-543X","issn":["0008-543X","1045-7410","1097-0142"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/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":"Cancer","raw_type":"journal-article"},{"id":"pmid:19402058","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/19402058","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":"Cancer","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1002/cncr.24234","doi":"https://doi.org/10.1002/cncr.24234","is_oa":true,"landing_page_url":"https://doi.org/10.1002/cncr.24234","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cncr.24234","source":{"id":"https://openalex.org/S126033908","display_name":"Cancer","issn_l":"0008-543X","issn":["0008-543X","1045-7410","1097-0142"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/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":"Cancer","raw_type":"journal-article"},"sustainable_development_goals":[{"score":1.0,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2086409166.pdf","grobid_xml":"https://content.openalex.org/works/W2086409166.grobid-xml"},"referenced_works_count":38,"referenced_works":["https://openalex.org/W1222874231","https://openalex.org/W1880480189","https://openalex.org/W1999966467","https://openalex.org/W2009334783","https://openalex.org/W2015644147","https://openalex.org/W2068555261","https://openalex.org/W2085295027","https://openalex.org/W2098176107","https://openalex.org/W2100669312","https://openalex.org/W2104540972","https://openalex.org/W2105677187","https://openalex.org/W2105984177","https://openalex.org/W2123769946","https://openalex.org/W2127768463","https://openalex.org/W2131473358","https://openalex.org/W2132689232","https://openalex.org/W2149026055","https://openalex.org/W2149456801","https://openalex.org/W2153867442","https://openalex.org/W2156408558","https://openalex.org/W2171469612","https://openalex.org/W2210929914","https://openalex.org/W2224540931","https://openalex.org/W2225151298","https://openalex.org/W2225644272","https://openalex.org/W2226364648","https://openalex.org/W2227609670","https://openalex.org/W2231449007","https://openalex.org/W2240204773","https://openalex.org/W2241079867","https://openalex.org/W2253554231","https://openalex.org/W2273695166","https://openalex.org/W2278754305","https://openalex.org/W2301603902","https://openalex.org/W2337968495","https://openalex.org/W2537427984","https://openalex.org/W2590359217","https://openalex.org/W4232325431"],"related_works":["https://openalex.org/W2170494050","https://openalex.org/W2073681230","https://openalex.org/W2265463209","https://openalex.org/W2068825538","https://openalex.org/W2171902233","https://openalex.org/W2612559621","https://openalex.org/W2327464088","https://openalex.org/W2063526820","https://openalex.org/W2169985261","https://openalex.org/W2126958845"],"abstract_inverted_index":{"Several":[0],"novel":[1],"therapies":[2],"have":[3,125,226],"been":[4,239],"approved":[5],"recently":[6],"in":[7,51,55,158,175,209,220],"advanced":[8],"renal":[9,231],"cell":[10],"carcinoma":[11],"(RCC).":[12],"These":[13],"agents":[14,75],"inhibit":[15],"pathways":[16,115],"downstream":[17],"of":[18,20,40,80,88,101,136,145,255],"loss":[19],"the":[21,28,81,134,253],"von":[22],"Hippel-Lindau":[23],"gene":[24],"VHL.":[25],"They":[26],"target":[27,39],"vascular":[29],"endothelial":[30],"growth":[31,105,110],"factor":[32,106,111],"(VEGF)":[33],"ligand,":[34],"VEGF":[35],"receptor":[36,107],"(VEGFR),":[37],"mammalian":[38],"rapamycin":[41],"(mTOR),":[42],"and":[43,162,213,229,251],"other":[44],"potentially":[45],"important":[46],"pathways.":[47],"Even":[48],"with":[49,92,103,128,151,172,188,194,198,211,222],"improvements":[50],"survival,":[52],"disease":[53],"progresses":[54],"all":[56,113,164],"patients.":[57],"There":[58],"is":[59,72,96,120],"a":[60,89],"critical":[61,244],"need":[62],"to":[63,76,245],"increase":[64],"complete":[65],"responses":[66,174],"(now":[67],"rare).":[68],"One":[69],"such":[70],"strategy":[71],"combining":[73,132],"several":[74],"block":[77],"different":[78],"levels":[79],"VEGF-VEGFR":[82,90],"axis":[83],"(vertical":[84],"blockade).":[85],"Alternatively,":[86],"combination":[87,129,236,256],"inhibitor":[91,95],"an":[93],"mTOR":[94],"attractive.":[97],"Finally,":[98],"horizontal":[99],"blockade":[100],"VEGFR":[102],"epidermal":[104],"and/or":[108],"platelet-derived":[109],"receptor,":[112],"signaling":[114],"activated":[116],"by":[117,203],"hypoxia-inducible":[118],"factor,":[119],"another":[121],"approach.":[122],"Already":[123],"trials":[124,250],"revealed":[126],"difficulties":[127],"therapy.":[130,259],"By":[131],"agents,":[133],"toxicity":[135,201],"1":[137,227],"or":[138,190,196],"both":[139],"can":[140],"be":[141,217,243],"enhanced.":[142],"The":[143],"authors":[144],"this":[146],"article":[147],"report":[148],"their":[149],"experience":[150],"sorafenib":[152],"plus":[153],"bevacizumab,":[154],"which":[155],"produced":[156],"increases":[157],"hand-foot":[159],"syndrome,":[160],"hypertension,":[161],"proteinuria,":[163],"known":[165],"toxic":[166],"effects.":[167],"Clinical":[168],"activity":[169],"was":[170],"impressive":[171],"25":[173],"48":[176],"patients":[177,221],"(52%":[178],"response":[179],"rate).":[180],"Other":[181],"combinations":[182],"also":[183],"required":[184],"dose":[185],"reductions":[186],"(sorafenib":[187],"temsirolimus)":[189],"were":[191],"intolerable":[192],"(sunitinib":[193],"temsirolimus":[195],"sunitinib":[197,212],"bevacizumab).":[199],"Unexpected":[200],"characterized":[202],"microangiopathic":[204],"hemolytic":[205],"anemia":[206],"occurred":[207],"late":[208],"treatment":[210],"bevacizumab.":[214],"Toxicity":[215],"may":[216],"more":[218],"severe":[219],"RCC,":[223],"who":[224],"frequently":[225],"kidney":[228],"poor":[230],"function.":[232],"Once":[233],"tolerability":[234],"for":[235],"regimens":[237],"has":[238],"established,":[240],"it":[241],"will":[242],"design":[246],"informative":[247],"phase":[248],"2":[249],"address":[252],"benefit":[254],"versus":[257],"sequential":[258]},"counts_by_year":[{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":1},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":3},{"year":2014,"cited_by_count":3},{"year":2013,"cited_by_count":7},{"year":2012,"cited_by_count":5}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}