{"id":"https://openalex.org/W2142525191","doi":null,"title":"ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells.","display_name":"ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells.","publication_year":2003,"publication_date":"2003-04-01","ids":{"openalex":"https://openalex.org/W2142525191","mag":"2142525191","pmid":"https://pubmed.ncbi.nlm.nih.gov/12684395"},"language":"en","primary_location":{"id":"pmid:12684395","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12684395","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":"Clinical cancer research : an official journal of the American Association for Cancer Research","raw_type":"Journal Article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["pubmed"],"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/A5040459072","display_name":"Judit Anido","orcid":"https://orcid.org/0000-0002-5569-8923","observed_orcids":["https://orcid.org/0000-0002-5569-8923"]},"institutions":[{"id":"https://openalex.org/I4210127641","display_name":"Vall d'Hebron Hospital Universitari","ror":"https://ror.org/03ba28x55","country_code":"ES","type":"healthcare","lineage":["https://openalex.org/I157913058","https://openalex.org/I4210127641","https://openalex.org/I4210153292"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Judit Anido","raw_affiliation_strings":["Laboratory of Oncology Research, Medical Oncology Service, Vall d'Hebron University Hospital, Barcelona 08035, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Oncology Research, Medical Oncology Service, Vall d'Hebron University Hospital, Barcelona 08035, Spain","institution_ids":["https://openalex.org/I4210127641"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064381901","display_name":"Pablo Matar","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Pablo Matar","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029048001","display_name":"Joan Albanell","orcid":"https://orcid.org/0000-0003-1239-4580","observed_orcids":["https://orcid.org/0000-0003-1239-4580"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Joan Albanell","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085170830","display_name":"Marta Guzm\u00e1n","orcid":"https://orcid.org/0000-0002-0924-9887","observed_orcids":["https://orcid.org/0000-0002-0924-9887"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Marta Guzm\u00e1n","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012974257","display_name":"Federico Rojo","orcid":"https://orcid.org/0000-0001-9989-0290","observed_orcids":["https://orcid.org/0000-0001-9989-0290"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Federico Rojo","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077169627","display_name":"Joaqu\u0131\u0301n Arribas","orcid":"https://orcid.org/0000-0002-0504-0664","observed_orcids":["https://orcid.org/0000-0002-0504-0664"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Joaquin Arribas","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000660231","display_name":"Steven D. Averbuch","orcid":"https://orcid.org/0000-0002-0210-5901","observed_orcids":["https://orcid.org/0000-0002-0210-5901"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Steve Averbuch","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5004300577","display_name":"Jose M Baselga","orcid":"https://orcid.org/0000-0003-1361-4063","observed_orcids":["https://orcid.org/0000-0003-1361-4063"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jose Baselga","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":14.166,"has_fulltext":false,"cited_by_count":247,"citation_normalized_percentile":{"value":0.99451308,"is_in_top_1_percent":true,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"9","issue":"4","first_page":"1274","last_page":"83"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10755","display_name":"HER2/EGFR in Cancer Research","score":1.0,"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/T10755","display_name":"HER2/EGFR in Cancer Research","score":1.0,"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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.0,"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","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/gefitinib","display_name":"gefitinib","score":0.9300000071525574},{"id":"https://openalex.org/keywords/egfr-tyrosine-kinase-inhibitors","display_name":"EGFR tyrosine kinase inhibitors","score":0.9269999861717224},{"id":"https://openalex.org/keywords/her2-overexpression","display_name":"HER2 overexpression","score":0.8830000162124634},{"id":"https://openalex.org/keywords/her3","display_name":"HER3","score":0.6859999895095825},{"id":"https://openalex.org/keywords/receptor-heterodimerization","display_name":"receptor heterodimerization","score":0.8939999938011169},{"id":"https://openalex.org/keywords/her2-her3-heterodimer","display_name":"HER2/HER3 heterodimer","score":0.7350000143051147},{"id":"https://openalex.org/keywords/bt474-cells","display_name":"BT474 cells","score":0.8259999752044678},{"id":"https://openalex.org/keywords/breast-cancer","display_name":"breast cancer","score":0.9309999942779541},{"id":"https://openalex.org/keywords/erbb-signaling-pathway","display_name":"ErbB signaling","score":0.7680000066757202},{"id":"https://openalex.org/keywords/growth-inhibition","display_name":"growth inhibition","score":0.44999998807907104}],"concepts":[{"id":"https://openalex.org/C185323287","wikidata":"https://www.wikidata.org/wiki/Q59252204","display_name":"Neuregulin","level":3,"score":0.8000900149345398},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.6746844053268433},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.639557957649231},{"id":"https://openalex.org/C2776362946","wikidata":"https://www.wikidata.org/wiki/Q424374","display_name":"Epidermal growth factor","level":3,"score":0.5515642762184143},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.5408440828323364},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5034865736961365},{"id":"https://openalex.org/C115456853","wikidata":"https://www.wikidata.org/wiki/Q17917132","display_name":"ERBB3","level":4,"score":0.45302197337150574},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.4169093072414398},{"id":"https://openalex.org/C2779786085","wikidata":"https://www.wikidata.org/wiki/Q412616","display_name":"Trastuzumab","level":4,"score":0.4129894971847534},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.4049980044364929},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3917490243911743},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.36964479088783264},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3589951694011688},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.31862470507621765},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.309917151927948},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.23992139101028442}],"mesh":[{"descriptor_ui":"D000077156","descriptor_name":"Gefitinib","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":true},{"descriptor_ui":"D001943","descriptor_name":"Breast Neoplasms","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002455","descriptor_name":"Cell Division","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004305","descriptor_name":"Dose-Response Relationship, Drug","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005434","descriptor_name":"Flow Cytometry","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":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010766","descriptor_name":"Phosphorylation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011233","descriptor_name":"Precipitin Tests","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011799","descriptor_name":"Quinazolines","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015153","descriptor_name":"Blotting, Western","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016650","descriptor_name":"Fluorescein-5-isothiocyanate","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017209","descriptor_name":"Apoptosis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018719","descriptor_name":"Erb-b2 Receptor Tyrosine Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D019281","descriptor_name":"Dimerization","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020890","descriptor_name":"Neuregulin-1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D020893","descriptor_name":"Receptor, ErbB-3","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true}],"locations_count":2,"locations":[{"id":"pmid:12684395","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12684395","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":"Clinical cancer research : an official journal of the American Association for Cancer Research","raw_type":"Journal Article"},{"id":"mag:2142525191","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12684395","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":null,"is_accepted":false,"is_published":false,"raw_source_name":"PubMed","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":49,"referenced_works":["https://openalex.org/W279429461","https://openalex.org/W1531775950","https://openalex.org/W1550092936","https://openalex.org/W1566737177","https://openalex.org/W1590794385","https://openalex.org/W1964321121","https://openalex.org/W1973188134","https://openalex.org/W1981108516","https://openalex.org/W1984681963","https://openalex.org/W1995993550","https://openalex.org/W2006752099","https://openalex.org/W2010174111","https://openalex.org/W2019691808","https://openalex.org/W2025357617","https://openalex.org/W2028151158","https://openalex.org/W2040264246","https://openalex.org/W2043363926","https://openalex.org/W2043471865","https://openalex.org/W2044868069","https://openalex.org/W2058586542","https://openalex.org/W2064047613","https://openalex.org/W2071033930","https://openalex.org/W2074356752","https://openalex.org/W2075962843","https://openalex.org/W2077374035","https://openalex.org/W2081441817","https://openalex.org/W2082117763","https://openalex.org/W2095483608","https://openalex.org/W2097072725","https://openalex.org/W2103002807","https://openalex.org/W2111004422","https://openalex.org/W2114291028","https://openalex.org/W2116323570","https://openalex.org/W2116398087","https://openalex.org/W2116401711","https://openalex.org/W2123206362","https://openalex.org/W2123284520","https://openalex.org/W2130840817","https://openalex.org/W2131362842","https://openalex.org/W2135938911","https://openalex.org/W2141393790","https://openalex.org/W2142848667","https://openalex.org/W2146404049","https://openalex.org/W2151127067","https://openalex.org/W2163002589","https://openalex.org/W2163402367","https://openalex.org/W2169635726","https://openalex.org/W2275508015","https://openalex.org/W2332928500"],"related_works":["https://openalex.org/W2131362842","https://openalex.org/W1590794385","https://openalex.org/W1980742775","https://openalex.org/W2071040849","https://openalex.org/W2142007492","https://openalex.org/W2129040492","https://openalex.org/W2130840817","https://openalex.org/W7100346751","https://openalex.org/W2138167831","https://openalex.org/W2007314461"],"abstract_inverted_index":{"PURPOSE:":[0],"ZD1839":[1,30,55,75,89,113,127,163,177,189,202,241],"is":[2,140,232],"a":[3,57,141,233],"tyrosine":[4,133],"kinase":[5,134],"inhibitor":[6,94],"of":[7,29,39,54,59,74,81,95,104,119,181,196,206,214,240],"the":[8,27,42,51,72,131,157,179,204,225],"epidermal":[9],"growth":[10,78,96,205],"factor":[11],"receptor":[12],"(EGFR)":[13],"that":[14,143,162,176,230],"has":[15],"shown":[16],"clinical":[17,238],"activity":[18],"against":[19],"EGFR-expressing":[20],"tumors.":[21,247],"Our":[22,227],"aim":[23],"was":[24,90],"to":[25,148,156,236],"explore":[26],"effects":[28,53,73],"in":[31,56,97,135,168,219,242],"breast":[32,60,67,98,110,208,246],"cancer":[33,68,99,111,209],"cell":[34,62,77],"lines":[35],"expressing":[36,101],"different":[37],"levels":[38,103],"EGFR":[40,105],"and":[41,79,85,106,116,122,137,150,185,193,216],"closely":[43],"related":[44],"HER2":[45,132,145,166,215],"receptor.":[46],"EXPERIMENTAL":[47],"DESIGN:":[48],"We":[49],"studied":[50,71],"growth-inhibitory":[52],"series":[58],"carcinoma":[61],"lines.":[63],"In":[64,108],"HER2-overexpressing":[65,207,245],"BT-474":[66,109],"cells,":[69,112,210],"we":[70,174],"on":[76],"heterodimerization":[80],"receptors":[82,121,218],"under":[83],"basal":[84,192],"ligand-stimulated":[86],"conditions.":[87],"RESULTS:":[88],"an":[91,220],"equally":[92],"potent":[93],"cells":[100],"high":[102],"HER2.":[107],"abolished":[114],"EGF-":[115],"heregulin-induced":[117,194],"activation":[118],"ErbB":[120],"downstream":[123],"signaling":[124],"molecules.":[125],"Because":[126],"does":[128,153],"not":[129,154],"inhibit":[130],"vitro,":[136],"because":[138],"heregulin":[139],"ligand":[142],"activates":[144],"by":[146,212],"binding":[147],"HER3":[149,217],"HER4":[151],"but":[152],"bind":[155],"EGFR,":[158],"our":[159],"findings":[160,228],"suggested":[161],"interfered":[164],"with":[165,224,244],"function":[167],"intact":[169],"cells.":[170],"Searching":[171],"for":[172],"mechanisms,":[173],"report":[175],"induces":[178],"formation":[180,195],"inactive":[182,221],"unphosphorylated":[183],"EGFR/HER2":[184],"EGFR/HER3":[186],"heterodimers.":[187,200],"Furthermore,":[188],"completely":[190],"abolishes":[191],"active":[197],"phosphorylated":[198],"HER2/HER3":[199],"CONCLUSIONS:":[201],"inhibits":[203],"possibly":[211],"sequestration":[213],"heterodimer":[222],"configuration":[223],"EGFR.":[226],"suggest":[229],"there":[231],"strong":[234],"rationale":[235],"conduct":[237],"trials":[239],"patients":[243]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":3},{"year":2022,"cited_by_count":3},{"year":2021,"cited_by_count":6},{"year":2020,"cited_by_count":5},{"year":2019,"cited_by_count":5},{"year":2018,"cited_by_count":6},{"year":2017,"cited_by_count":8},{"year":2016,"cited_by_count":4},{"year":2015,"cited_by_count":11},{"year":2014,"cited_by_count":9},{"year":2013,"cited_by_count":12},{"year":2012,"cited_by_count":7}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}
