{"id":"https://openalex.org/W2497089919","doi":"https://doi.org/10.1002/9781118468678.ch2","title":"Combining Targeted Therapies","display_name":"Combining Targeted Therapies","publication_year":2015,"publication_date":"2015-10-19","ids":{"openalex":"https://openalex.org/W2497089919","doi":"https://doi.org/10.1002/9781118468678.ch2","mag":"2497089919"},"language":"en","primary_location":{"id":"doi:10.1002/9781118468678.ch2","doi":"https://doi.org/10.1002/9781118468678.ch2","is_oa":false,"landing_page_url":"https://doi.org/10.1002/9781118468678.ch2","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Targeted Therapy in Translational Cancer Research","raw_type":"other"},"volume":{"id":"https://openalex.org/W2344718881","display_name":"Targeted Therapy in Translational Cancer Research"},"type":"other","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/A5031165814","display_name":"Jordi Ahnert Rodon","orcid":"https://orcid.org/0000-0001-6467-3632","observed_orcids":["https://orcid.org/0000-0001-6467-3632","https://orcid.org/0000-0003-2234-5248"]},"institutions":[{"id":"https://openalex.org/I123044942","display_name":"Universitat Aut\u00f2noma de Barcelona","ror":"https://ror.org/052g8jq94","country_code":"ES","type":"education","lineage":["https://openalex.org/I123044942"]},{"id":"https://openalex.org/I4387155398","display_name":"Vall d'Hebron Institute of Oncology","ror":"https://ror.org/054xx3904","country_code":"ES","type":"healthcare","lineage":["https://openalex.org/I4387153040","https://openalex.org/I4387155398"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Jordi Rodon1","raw_affiliation_strings":["Early Clinical Drug Development Group, Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Early Clinical Drug Development Group, Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain","institution_ids":["https://openalex.org/I123044942","https://openalex.org/I4387155398"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112385468","display_name":"Anal\u00eda Azaro","orcid":"https://orcid.org/0000-0001-6852-4925","observed_orcids":["https://orcid.org/0000-0001-6852-4925"]},"institutions":[{"id":"https://openalex.org/I123044942","display_name":"Universitat Aut\u00f2noma de Barcelona","ror":"https://ror.org/052g8jq94","country_code":"ES","type":"education","lineage":["https://openalex.org/I123044942"]},{"id":"https://openalex.org/I4387155398","display_name":"Vall d'Hebron Institute of Oncology","ror":"https://ror.org/054xx3904","country_code":"ES","type":"healthcare","lineage":["https://openalex.org/I4387153040","https://openalex.org/I4387155398"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Analia Azaro1","raw_affiliation_strings":["Early Clinical Drug Development Group, Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Early Clinical Drug Development Group, Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain","institution_ids":["https://openalex.org/I123044942","https://openalex.org/I4387155398"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062326140","display_name":"Davis Yuri Torrejon","orcid":"https://orcid.org/0000-0002-4864-6236","observed_orcids":["https://orcid.org/0000-0002-4864-6236"]},"institutions":[{"id":"https://openalex.org/I123044942","display_name":"Universitat Aut\u00f2noma de Barcelona","ror":"https://ror.org/052g8jq94","country_code":"ES","type":"education","lineage":["https://openalex.org/I123044942"]},{"id":"https://openalex.org/I4387155398","display_name":"Vall d'Hebron Institute of Oncology","ror":"https://ror.org/054xx3904","country_code":"ES","type":"healthcare","lineage":["https://openalex.org/I4387153040","https://openalex.org/I4387155398"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Davis Torrejon1,","raw_affiliation_strings":["Early Clinical Drug Development Group, Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Early Clinical Drug Development Group, Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain","institution_ids":["https://openalex.org/I123044942","https://openalex.org/I4387155398"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5053481267","display_name":"Razelle Kurzrock","orcid":"https://orcid.org/0000-0003-4110-1214","observed_orcids":["https://orcid.org/0000-0003-4110-1214"]},"institutions":[{"id":"https://openalex.org/I4390039236","display_name":"Moores Cancer Center","ror":"https://ror.org/01qkmtm61","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2800935791","https://openalex.org/I36258959","https://openalex.org/I4390039236"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Razelle Kurzrock","raw_affiliation_strings":["Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, CA, USA","institution_ids":["https://openalex.org/I4390039236"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"14","last_page":"26"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.49880000948905945,"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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.49880000948905945,"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/T11235","display_name":"Statistical Methods in Clinical Trials","score":0.1096000000834465,"subfield":{"id":"https://openalex.org/subfields/2613","display_name":"Statistics and Probability"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.0697999969124794,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/combination-targeted-therapy","display_name":"combination targeted therapy","score":0.722000002861023},{"id":"https://openalex.org/keywords/multikinase-inhibitor","display_name":"multikinase inhibitor","score":0.9670000076293945},{"id":"https://openalex.org/keywords/tumor-resistance-mechanisms","display_name":"tumor resistance mechanisms","score":0.7509999871253967},{"id":"https://openalex.org/keywords/synthetic-lethality","display_name":"synthetic lethality","score":0.8159999847412109},{"id":"https://openalex.org/keywords/phase-i-trial-design","display_name":"phase I trial design","score":0.8529999852180481},{"id":"https://openalex.org/keywords/personalized-medicine","display_name":"personalized medicine","score":0.5550000071525574},{"id":"https://openalex.org/keywords/tumor-heterogeneity","display_name":"tumor heterogeneity","score":0.6759999990463257},{"id":"https://openalex.org/keywords/feedback-loops","display_name":"feedback loops","score":0.5270000100135803},{"id":"https://openalex.org/keywords/translational-research","display_name":"translational research","score":0.46299999952316284}],"concepts":[{"id":"https://openalex.org/C68762167","wikidata":"https://www.wikidata.org/wiki/Q910164","display_name":"Cheminformatics","level":2,"score":0.6028230786323547},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.5366731286048889},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4831113815307617},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4530659317970276},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.4496949315071106},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3937002718448639},{"id":"https://openalex.org/C112930515","wikidata":"https://www.wikidata.org/wiki/Q4389547","display_name":"Risk analysis (engineering)","level":1,"score":0.3696141242980957},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.36301904916763306},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.22909703850746155}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1002/9781118468678.ch2","doi":"https://doi.org/10.1002/9781118468678.ch2","is_oa":false,"landing_page_url":"https://doi.org/10.1002/9781118468678.ch2","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Targeted Therapy in Translational Cancer Research","raw_type":"other"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9391000270843506,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[{"score":0.8100000023841858,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":121,"referenced_works":["https://openalex.org/W110572178","https://openalex.org/W207907705","https://openalex.org/W1539571840","https://openalex.org/W1963482033","https://openalex.org/W1963493384","https://openalex.org/W1966182052","https://openalex.org/W1966803171","https://openalex.org/W1968137491","https://openalex.org/W1970434896","https://openalex.org/W1972852140","https://openalex.org/W1988104771","https://openalex.org/W1991384876","https://openalex.org/W1996234795","https://openalex.org/W1996715118","https://openalex.org/W1998971866","https://openalex.org/W1999065747","https://openalex.org/W2000980666","https://openalex.org/W2001343031","https://openalex.org/W2004492241","https://openalex.org/W2014557438","https://openalex.org/W2014881369","https://openalex.org/W2015244046","https://openalex.org/W2015512041","https://openalex.org/W2020372547","https://openalex.org/W2022768088","https://openalex.org/W2028959752","https://openalex.org/W2031585970","https://openalex.org/W2032211985","https://openalex.org/W2035240798","https://openalex.org/W2040956995","https://openalex.org/W2041221416","https://openalex.org/W2043058822","https://openalex.org/W2043714862","https://openalex.org/W2044025814","https://openalex.org/W2048440423","https://openalex.org/W2052874737","https://openalex.org/W2059890247","https://openalex.org/W2061708072","https://openalex.org/W2061827267","https://openalex.org/W2064876347","https://openalex.org/W2066128027","https://openalex.org/W2066168802","https://openalex.org/W2067653691","https://openalex.org/W2067933166","https://openalex.org/W2069640477","https://openalex.org/W2070705072","https://openalex.org/W2072174281","https://openalex.org/W2089288294","https://openalex.org/W2091582819","https://openalex.org/W2094882473","https://openalex.org/W2097742807","https://openalex.org/W2100614336","https://openalex.org/W2100808408","https://openalex.org/W2101293925","https://openalex.org/W2102095362","https://openalex.org/W2103445331","https://openalex.org/W2104573784","https://openalex.org/W2106350749","https://openalex.org/W2106789440","https://openalex.org/W2111065680","https://openalex.org/W2111578514","https://openalex.org/W2112046350","https://openalex.org/W2113760232","https://openalex.org/W2114029270","https://openalex.org/W2114260801","https://openalex.org/W2114622977","https://openalex.org/W2116376943","https://openalex.org/W2116566535","https://openalex.org/W2117280704","https://openalex.org/W2118371851","https://openalex.org/W2120043042","https://openalex.org/W2120468520","https://openalex.org/W2120492882","https://openalex.org/W2120519038","https://openalex.org/W2121198752","https://openalex.org/W2122088232","https://openalex.org/W2123532766","https://openalex.org/W2124757685","https://openalex.org/W2124886112","https://openalex.org/W2125130429","https://openalex.org/W2126042521","https://openalex.org/W2126783165","https://openalex.org/W2127933711","https://openalex.org/W2128373232","https://openalex.org/W2128905862","https://openalex.org/W2128923437","https://openalex.org/W2129172946","https://openalex.org/W2131351052","https://openalex.org/W2131413118","https://openalex.org/W2133296598","https://openalex.org/W2135131549","https://openalex.org/W2136146667","https://openalex.org/W2136791645","https://openalex.org/W2137600224","https://openalex.org/W2138977668","https://openalex.org/W2139135964","https://openalex.org/W2139225734","https://openalex.org/W2139511378","https://openalex.org/W2140512094","https://openalex.org/W2142046859","https://openalex.org/W2143163879","https://openalex.org/W2148971037","https://openalex.org/W2152829742","https://openalex.org/W2154200023","https://openalex.org/W2156078931","https://openalex.org/W2157769714","https://openalex.org/W2158780525","https://openalex.org/W2160565595","https://openalex.org/W2161289668","https://openalex.org/W2161375781","https://openalex.org/W2161422104","https://openalex.org/W2162423163","https://openalex.org/W2170655985","https://openalex.org/W2171608750","https://openalex.org/W2171676198","https://openalex.org/W2171708713","https://openalex.org/W2172265576","https://openalex.org/W2318605753","https://openalex.org/W2938564540","https://openalex.org/W4231550722","https://openalex.org/W6604485291"],"related_works":["https://openalex.org/W2133198677","https://openalex.org/W2416603274","https://openalex.org/W2767168338","https://openalex.org/W2110646396","https://openalex.org/W2277678393","https://openalex.org/W2471562228","https://openalex.org/W4311247426","https://openalex.org/W7119506977","https://openalex.org/W3210116582","https://openalex.org/W2002548537"],"abstract_inverted_index":{"Numerous":[0],"practical":[1],"issues":[2,163,192],"must":[3,219],"be":[4,220],"considered":[5],"when":[6],"combining":[7,145,256],"targeted":[8,257],"therapies":[9,32,258],"in":[10,144,182,268],"early":[11],"clinical":[12,186,244],"drug":[13,208,210],"development.":[14],"These":[15],"include":[16,43],"tumor":[17],"resistance":[18],"mechanisms,":[19],"the":[20,28,44,65,90,111,114,119,178,204,241,265],"existence":[21],"of":[22,30,46,62,67,92,180,206,243],"multiple,":[23],"redundant":[24],"signaling":[25],"pathways,":[26,150],"and":[27,58,79,94,102,105,153,156,177,193,225,237,246],"failure":[29],"single-agent":[31],"to":[33,39,87,107,113,129,172,185,228],"achieve":[34],"cures.":[35],"The":[36],"strategies":[37,140],"adopted":[38],"examine":[40],"combinatorial":[41,77,252],"therapy":[42],"goal":[45],"hitting":[47],"more":[48],"than":[49],"one":[50],"target":[51,167],"by":[52,73],"specifically":[53],"inhibiting":[54,151],"signal":[55],"transduction":[56],"cascades":[57],"suppressing":[59],"specific":[60],"mechanisms":[61],"action":[63],"with":[64,175,259],"use":[66],"multitargeted":[68],"kinase":[69],"inhibitors":[70],"made":[71],"possible":[72],"high-throughput":[74],"screening":[75],"techniques,":[76],"chemistry,":[78],"chemoinformatics.":[80],"Two":[81],"complex":[82],"considerations":[83],"are:":[84,164],"which":[85,226],"agents":[86],"combine":[88,173],"given":[89,264],"heterogeneity":[91],"tumors":[93],"their":[95],"various":[96,195],"underlying":[97],"perturbations,":[98],"including":[99,147],"secondary":[100],"mutations":[101],"feedback":[103],"loops,":[104],"how":[106,171,223],"translate":[108],"findings":[109],"from":[110,118],"bench":[112],"bedside":[115],"or":[116,209],"directly":[117],"bedside.":[120],"Another":[121],"consideration":[122],"is:":[123],"When":[124],"is":[125,222],"there":[126],"enough":[127],"information":[128],"provide":[130],"a":[131,135,158,207],"rationale":[132],"for":[133,169,202,212],"instituting":[134],"phase":[136],"I":[137],"trial?":[138],"Various":[139],"have":[141],"been":[142],"used":[143],"molecules,":[146],"targeting":[148],"diverse":[149],"upstream":[152],"downstream":[154],"signals,":[155],"adopting":[157],"synthetic":[159],"lethality":[160],"paradigm.":[161],"Other":[162],"determining":[165,203],"appropriate":[166],"populations":[168],"treatment,":[170],"therapeutics":[174],"diagnostics,":[176],"frequency":[179],"targets":[181],"patients":[183],"referred":[184],"trials.":[187],"Here,":[188],"we":[189],"review":[190],"these":[191,249],"propose":[194],"novel":[196],"trial":[197],"designs":[198],"that":[199,218],"are":[200],"logical":[201],"efficacy":[205],"combination":[211],"personalized":[213],"treatment.":[214,253],"A":[215],"difficult":[216],"issue":[217],"answered":[221],"many":[224],"drugs":[227],"combine.":[229],"Recent":[230],"technologies,":[231],"such":[232],"as":[233],"multiplexed":[234],"assay":[235],"platforms":[236],"bioinformatics,":[238],"will":[239],"shape":[240],"future":[242],"trials":[245],"help":[247],"answer":[248],"questions":[250],"surrounding":[251],"In":[254],"addition,":[255],"immunotherapy":[260],"requires":[261],"special":[262],"attention,":[263],"recent":[266],"developments":[267],"both":[269],"fields.":[270]},"counts_by_year":[],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2016-08-23T00:00:00"}