{"id":"https://openalex.org/W2052180940","doi":"https://doi.org/10.1158/1538-7445.am2013-3527","title":"Abstract 3527: Assessing signal modulation in preclinical models and tumor tissue from patients enrolled in a Phase 1 study of the HER3/EGFR dual action antibody, MEHD7945A (MEHD), as an exploratory pharmacodynamic (PD) analysis.","display_name":"Abstract 3527: Assessing signal modulation in preclinical models and tumor tissue from patients enrolled in a Phase 1 study of the HER3/EGFR dual action antibody, MEHD7945A (MEHD), as an exploratory pharmacodynamic (PD) analysis.","publication_year":2013,"publication_date":"2013-04-01","ids":{"openalex":"https://openalex.org/W2052180940","doi":"https://doi.org/10.1158/1538-7445.am2013-3527","mag":"2052180940"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2013-3527","doi":"https://doi.org/10.1158/1538-7445.am2013-3527","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2013-3527","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/A5090977353","display_name":"Elicia M. Penuel","orcid":"https://orcid.org/0000-0001-7285-1929","observed_orcids":["https://orcid.org/0000-0001-7285-1929"]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Elicia M. Penuel","raw_affiliation_strings":["1Genentech, South San Francisco, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Genentech, South San Francisco, CA;","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006474645","display_name":"Luciana Burton","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Luciana Burton","raw_affiliation_strings":["1Genentech, South San Francisco, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Genentech, South San Francisco, CA;","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028575353","display_name":"Howard Marvin Stern","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210108457","display_name":"Infinity Pharmaceuticals (United States)","ror":"https://ror.org/01sfsq511","country_code":"US","type":"company","lineage":["https://openalex.org/I4210108457"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Howard Stern","raw_affiliation_strings":["2Molecular Pathology at Infinity Pharmaceuticals, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Molecular Pathology at Infinity Pharmaceuticals, MA","institution_ids":["https://openalex.org/I4210108457"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042199271","display_name":"Lackner Mark","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lackner Mark","raw_affiliation_strings":["1Genentech, South San Francisco, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Genentech, South San Francisco, CA;","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020637647","display_name":"Andrea Pirzkall","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Andrea Pirzkall","raw_affiliation_strings":["1Genentech, South San Francisco, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Genentech, South San Francisco, CA;","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036391595","display_name":"Lukas C. Amler","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lukas Amler","raw_affiliation_strings":["1Genentech, South San Francisco, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Genentech, South San Francisco, CA;","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5086221671","display_name":"Gabriele Schaefer","orcid":"https://orcid.org/0000-0001-9727-3555","observed_orcids":["https://orcid.org/0000-0001-9727-3555"]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gabriele Schaefer","raw_affiliation_strings":["1Genentech, South San Francisco, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Genentech, South San Francisco, CA;","institution_ids":["https://openalex.org/I183934855"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"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":"73","issue":"8_Supplement","first_page":"3527","last_page":"3527"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.9990000128746033,"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":0.9990000128746033,"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":0.0005000000237487257,"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":0.00019999999494757503,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/pharmacodynamic-markers","display_name":"pharmacodynamic biomarkers","score":0.7429999709129333},{"id":"https://openalex.org/keywords/ras-mapk-pathway","display_name":"RAS/MAPK pathway","score":0.7820000052452087},{"id":"https://openalex.org/keywords/pi3k-akt-signaling","display_name":"PI3K/Akt signaling","score":0.9959999918937683},{"id":"https://openalex.org/keywords/mapk-phosphorylation","display_name":"MAPK phosphorylation","score":0.8009999990463257},{"id":"https://openalex.org/keywords/ribosomal-protein-s6-phosphorylation","display_name":"S6 phosphorylation","score":0.875},{"id":"https://openalex.org/keywords/pras40-phosphorylation","display_name":"PRAS40 phosphorylation","score":0.9800000190734863},{"id":"https://openalex.org/keywords/xenograft-models","display_name":"xenograft models","score":0.6809999942779541},{"id":"https://openalex.org/keywords/her3","display_name":"HER3","score":0.4440000057220459},{"id":"https://openalex.org/keywords/egfr","display_name":"EGFR","score":0.9660000205039978},{"id":"https://openalex.org/keywords/tumor-growth-inhibition","display_name":"tumor growth inhibition","score":0.753000020980835}],"concepts":[{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.7078499794006348},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.7001054286956787},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.6119107007980347},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.6075423955917358},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.5660688877105713},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5455089211463928},{"id":"https://openalex.org/C2776415932","wikidata":"https://www.wikidata.org/wiki/Q48743","display_name":"Western blot","level":3,"score":0.4971511662006378},{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.48254650831222534},{"id":"https://openalex.org/C555283112","wikidata":"https://www.wikidata.org/wiki/Q1637543","display_name":"Carcinogenesis","level":3,"score":0.4348160922527313},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.41741201281547546},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.39352431893348694},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.36497336626052856},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3596094250679016},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3579888939857483},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.18182623386383057},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.14363381266593933},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2013-3527","doi":"https://doi.org/10.1158/1538-7445.am2013-3527","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2013-3527","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":[{"display_name":"Good health and well-being","score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3"}],"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/W2316945429","https://openalex.org/W1989235405","https://openalex.org/W1992478608","https://openalex.org/W7099286770","https://openalex.org/W2319126619","https://openalex.org/W2085690948","https://openalex.org/W2065759895","https://openalex.org/W2125457616","https://openalex.org/W2158819778","https://openalex.org/W2110933411"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Aberrant":[2],"activation":[3],"of":[4,32,86,97,104,150,183,192,222,335,347,367,375,444,461,466],"HER":[5],"family":[6],"members":[7],"including":[8,216],"EGFR":[9,47,193,242,248,258,274,390],"results":[10],"in":[11,16,107,124,136,175,202,224,253,255,285,294,304,352,378,394,402,430,439],"unregulated":[12],"proliferative":[13],"signals":[14],"involved":[15],"tumorigenesis.":[17],"HER3":[18,49,195,260,388],"plays":[19],"a":[20,25,39,314,440],"unique":[21],"role":[22],"as":[23,264,313,364,452],"both":[24,257,286],"dimerization-dependent":[26],"allosteric":[27],"catalyst":[28],"and":[29,48,64,82,110,119,128,145,155,165,173,206,218,227,259,302,326,330,349,356,362,371,433],"critical":[30,88],"activator":[31],"PI3":[33],"kinase":[34],"signaling":[35,52,70,89,105,185,197,223,252,284,351,384],"(PI3K).":[36],"MEHD":[37,140,147,199,278,293,311,368,398],"is":[38,399],"dual-action":[40],"antibody":[41],"that":[42,235,289,383,397],"blocks":[43],"ligand":[44,74,98],"binding":[45,75],"to":[46,50,76,94],"abrogate":[51],"downstream":[53],"from":[54,134,241,308,436],"these":[55,77,87,295,376],"two":[56,68],"receptors.":[57],"Early":[58],"clinical":[59],"evidence":[60],"shows":[61],"PD":[62,315],"modulation":[63,429],"biological":[65,372],"activity.":[66,101,373],"The":[67],"major":[69],"pathways":[71,112,229,385],"activated":[72,196],"by":[73,115,188,198,209,230,238,247,266,273,292,300,340],"receptors":[78],"are":[79,392],"the":[80,108,137,168,225,309,445,462,467],"RAS/MAPK":[81,109,226,348],"PI3K/AKT":[83,111,228,350],"pathways.":[84],"Phosphorylation":[85,103],"proteins":[90,106],"can":[91],"be":[92],"monitored":[93],"evaluate":[95],"inhibition":[96,249,275,391],"driven":[99,243],"receptor":[100],"Methods":[102],"was":[113,153,171,200,245,279],"measured":[114,299],"Western":[116],"blot":[117,211],"analysis":[118,182,212,221],"reverse-phase":[120],"protein":[121],"arrays":[122],"(RPPA)":[123],"MEHD-sensitive":[125,353],"cell":[126,204,354],"lines":[127,205,355],"xenograft":[129,207,357],"models.":[130,287],"Paired":[131],"tumor":[132,267,327,380,434],"biopsies":[133,319,381],"patients":[135,403,437],"Phase":[138,441],"1":[139,442],"study":[141,312,443],"were":[142,236,261,270,290,298,320],"collected":[143],"pre":[144],"post":[146],"dosing.":[148],"Half":[149],"each":[151],"sample":[152],"formalin-fixed":[154],"paraffin-embedded":[156],"for":[157,181,213,328,470],"immunohistochemistry":[158],"(IHC)":[159],"using":[160],"pS6":[161,339,363],"(S235/236),":[162],"pPRAS40":[163],"(T246),":[164],"pMAPK":[166,217],"(T202/Y204);":[167],"other":[169],"half":[170],"frozen":[172],"embedded":[174],"Optimum":[176],"Cutting":[177],"Temperature":[178],"compound":[179],"(OCT)":[180],"multiple":[184],"pathway":[186],"endpoints":[187],"RPPA.":[189,343],"Results":[190],"Inhibition":[191],"and/or":[194,342,389],"confirmed":[201],"sensitive":[203],"models":[208,244,254,297,358,432],"western":[210],"key":[214],"analytes":[215],"pS6.":[219],"Broader":[220],"RPPA":[231,301],"demonstrated":[232,382],"additional":[233],"markers":[234,377],"inhibited":[237,272,291],"MEHD.":[239],"Signaling":[240],"blocked":[246],"alone":[250],"but":[251],"which":[256],"contributing":[262],"factors,":[263],"assessed":[265],"growth":[268],"inhibition,":[269],"not":[271],"alone.":[276],"However,":[277],"equally":[280],"effective":[281],"at":[282],"blocking":[283],"Analytes":[288],"pre-clinical":[296],"IHC":[303,341],"paired":[305,318],"biopsy":[306],"specimens":[307],"Ph1":[310],"assessment.":[316],"Thirty-two":[317],"obtained.":[321],"20/32":[322],"had":[323],"sufficient":[324],"tissue":[325,435],"assessment":[329],"11/20":[331],"showed":[332],"decreased":[333],"phosphorylation":[334],"pERK,":[336,360],"pPRAS40,":[337,361],"or":[338],"Conclusions":[344],"Preclinical":[345],"evaluation":[346],"identified":[359],"measurable":[365],"indicators":[366],"target":[369],"engagement":[370],"Evaluation":[374],"patient":[379],"consistent":[386],"with":[387],"downregulated":[393],"tumors,":[395],"suggesting":[396],"biologically":[400],"active":[401],"(see":[404],"Juric":[405],"et":[406],"al.,":[407],"AACR":[408],"abstract).":[409],"Citation":[410],"Format:":[411],"Elicia":[412],"M.":[413],"Penuel,":[414],"Luciana":[415],"Burton,":[416],"Howard":[417],"Stern,":[418],"Lackner":[419],"Mark,":[420],"Andrea":[421],"Pirzkall,":[422],"Lukas":[423],"Amler,":[424],"Gabriele":[425],"Schaefer.":[426],"Assessing":[427],"signal":[428],"preclinical":[431],"enrolled":[438],"HER3/EGFR":[446],"dual":[447],"action":[448],"antibody,":[449],"MEHD7945A":[450],"(MEHD),":[451],"an":[453],"exploratory":[454],"pharmacodynamic":[455],"(PD)":[456],"analysis.":[457],"[abstract].":[458],"In:":[459],"Proceedings":[460],"104th":[463],"Annual":[464],"Meeting":[465],"American":[468],"Association":[469],"Cancer":[471,481],"Research;":[472],"2013":[473],"Apr":[474],"6-10;":[475],"Washington,":[476],"DC.":[477],"Philadelphia":[478],"(PA):":[479],"AACR;":[480],"Res":[482],"2013;73(8":[483],"Suppl):Abstract":[484],"nr":[485],"3527.":[486],"doi:10.1158/1538-7445.AM2013-3527":[487]},"counts_by_year":[],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2016-06-24T00:00:00"}