{"id":"https://openalex.org/W7225168332","doi":"https://doi.org/10.1136/jitc-2026-sitc2026.1105","title":"1105 HER3 inhibition sensitizes metastatic colorectal and pancreatic cancer to immunotherapy","display_name":"1105 HER3 inhibition sensitizes metastatic colorectal and pancreatic cancer to immunotherapy","publication_year":2026,"publication_date":"2026-11-01","ids":{"openalex":"https://openalex.org/W7225168332","doi":"https://doi.org/10.1136/jitc-2026-sitc2026.1105"},"language":"en","primary_location":{"id":"doi:10.1136/jitc-2026-sitc2026.1105","doi":"https://doi.org/10.1136/jitc-2026-sitc2026.1105","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2026-sitc2026.1105","pdf_url":"https://jitc.bmj.com/content/14/Suppl_2/A1265.full.pdf","source":{"id":"https://openalex.org/S2754803477","display_name":"Journal for ImmunoTherapy of Cancer","issn_l":"2051-1426","issn":["2051-1426"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319945","host_organization_name":"BMJ","host_organization_lineage":["https://openalex.org/P4310319945"],"host_organization_lineage_names":["BMJ"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Regular Abstracts","raw_type":"proceedings-article"},"volume":null,"type":"conference-abstract","is_traditional":false,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://jitc.bmj.com/content/14/Suppl_2/A1265.full.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5132844774","display_name":"Chao Wei","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Chao Wei","raw_affiliation_strings":["Case Western Reserve University School of Medicine, Cleveland, OH, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Case Western Reserve University School of Medicine, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006216872","display_name":"Moeez Ghani Rathore","orcid":"https://orcid.org/0000-0002-0999-0747","observed_orcids":["https://orcid.org/0000-0002-0999-0747"]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Moeez Rathore","raw_affiliation_strings":["Case Western Reserve University School of Medicine, Cleveland, OH, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Case Western Reserve University School of Medicine, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050049106","display_name":"Elizabeth Bryson","orcid":"https://orcid.org/0000-0001-7521-2532","observed_orcids":["https://orcid.org/0000-0001-7521-2532"]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Elizabeth Bryson","raw_affiliation_strings":["Case Western Reserve University School of Medicine, Cleveland, OH, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Case Western Reserve University School of Medicine, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011170641","display_name":"Kimberly Curry","orcid":"https://orcid.org/0009-0006-8703-620X","observed_orcids":["https://orcid.org/0009-0006-8703-620X"]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kimberly Curry","raw_affiliation_strings":["Case Western Reserve University School of Medicine, Cleveland, OH, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Case Western Reserve University School of Medicine, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5091002849","display_name":"Jordan R. Winter","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210108791","display_name":"University Hospitals Cleveland Medical Center","ror":"https://ror.org/01gc0wp38","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799343972","https://openalex.org/I4210108791"]},{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jordan Winter","raw_affiliation_strings":["Case Western Reserve University School of Medicine, Cleveland, OH, USA","University Hospitals Cleveland Medical Center, Cleveland, OH, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Case Western Reserve University School of Medicine, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]},{"raw_affiliation_string":"University Hospitals Cleveland Medical Center, Cleveland, OH, USA","institution_ids":["https://openalex.org/I4210108791"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5160441587","display_name":"Rui Wang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210108791","display_name":"University Hospitals Cleveland Medical Center","ror":"https://ror.org/01gc0wp38","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799343972","https://openalex.org/I4210108791"]},{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rui Wang","raw_affiliation_strings":["Case Western Reserve University School of Medicine, Cleveland, OH, USA","University Hospitals Cleveland Medical Center, Cleveland, OH, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Case Western Reserve University School of Medicine, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]},{"raw_affiliation_string":"University Hospitals Cleveland Medical Center, Cleveland, OH, USA","institution_ids":["https://openalex.org/I4210108791"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":2490,"currency":"USD","value_usd":2490},"apc_paid":{"value":2490,"currency":"USD","value_usd":2490},"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"A1265","last_page":"A1266"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9731000065803528,"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9731000065803528,"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/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.006500000134110451,"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"}},{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.005900000222027302,"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-colorectal-cancer","display_name":"metastatic colorectal cancer","score":0.9660000205039978},{"id":"https://openalex.org/keywords/pancreatic-cancer","display_name":"pancreatic cancer","score":0.9520000219345093},{"id":"https://openalex.org/keywords/liver-metastases","display_name":"liver metastasis","score":0.8330000042915344},{"id":"https://openalex.org/keywords/immune-checkpoint-inhibitors","display_name":"immune checkpoint inhibitors","score":0.7730000019073486},{"id":"https://openalex.org/keywords/anti-pd-1-combination-therapy","display_name":"anti-PD-1 combination therapy","score":0.8629999756813049},{"id":"https://openalex.org/keywords/immunotherapy-resistance","display_name":"immunotherapy resistance","score":0.6420000195503235},{"id":"https://openalex.org/keywords/metabolic-reprogramming","display_name":"metabolic reprogramming","score":0.7910000085830688},{"id":"https://openalex.org/keywords/glycolysis","display_name":"glycolysis","score":0.8809999823570251},{"id":"https://openalex.org/keywords/lactate","display_name":"lactate","score":0.8059999942779541},{"id":"https://openalex.org/keywords/cd8-t-cell-exhaustion","display_name":"CD8+ T cell exhaustion","score":0.8539999723434448},{"id":"https://openalex.org/keywords/tox","display_name":"TOX","score":0.7620000243186951},{"id":"https://openalex.org/keywords/phosphofructokinase-2","display_name":"phosphofructokinase-2","score":0.8130000233650208},{"id":"https://openalex.org/keywords/neuregulin-1","display_name":"neuregulin-1","score":0.6190000176429749},{"id":"https://openalex.org/keywords/lrg1","display_name":"LRG1","score":0.7900000214576721}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8450999855995178},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.6923999786376953},{"id":"https://openalex.org/C2780210213","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic cancer","level":3,"score":0.6657999753952026},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.5612999796867371},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.532800018787384},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.4507000148296356},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.40310001373291016},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.36250001192092896},{"id":"https://openalex.org/C144369459","wikidata":"https://www.wikidata.org/wiki/Q182517","display_name":"CA19-9","level":4,"score":0.33559998869895935},{"id":"https://openalex.org/C2779013556","wikidata":"https://www.wikidata.org/wiki/Q181876","display_name":"Metastasis","level":3,"score":0.32260000705718994},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.28940001130104065},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.2892000079154968},{"id":"https://openalex.org/C2780790343","wikidata":"https://www.wikidata.org/wiki/Q5090610","display_name":"Chemoimmunotherapy","level":4,"score":0.28679999709129333},{"id":"https://openalex.org/C2777996000","wikidata":"https://www.wikidata.org/wiki/Q7130412","display_name":"Pancreatic tumor","level":4,"score":0.2628999948501587},{"id":"https://openalex.org/C71472368","wikidata":"https://www.wikidata.org/wiki/Q676880","display_name":"Text mining","level":2,"score":0.26179999113082886}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1136/jitc-2026-sitc2026.1105","doi":"https://doi.org/10.1136/jitc-2026-sitc2026.1105","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2026-sitc2026.1105","pdf_url":"https://jitc.bmj.com/content/14/Suppl_2/A1265.full.pdf","source":{"id":"https://openalex.org/S2754803477","display_name":"Journal for ImmunoTherapy of Cancer","issn_l":"2051-1426","issn":["2051-1426"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319945","host_organization_name":"BMJ","host_organization_lineage":["https://openalex.org/P4310319945"],"host_organization_lineage_names":["BMJ"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Regular Abstracts","raw_type":"proceedings-article"}],"best_oa_location":{"id":"doi:10.1136/jitc-2026-sitc2026.1105","doi":"https://doi.org/10.1136/jitc-2026-sitc2026.1105","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2026-sitc2026.1105","pdf_url":"https://jitc.bmj.com/content/14/Suppl_2/A1265.full.pdf","source":{"id":"https://openalex.org/S2754803477","display_name":"Journal for ImmunoTherapy of Cancer","issn_l":"2051-1426","issn":["2051-1426"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319945","host_organization_name":"BMJ","host_organization_lineage":["https://openalex.org/P4310319945"],"host_organization_lineage_names":["BMJ"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Regular Abstracts","raw_type":"proceedings-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":1.0}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225168332.pdf","grobid_xml":"https://content.openalex.org/works/W7225168332.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7148787815","https://openalex.org/W3198541603","https://openalex.org/W3197158693","https://openalex.org/W2012951781","https://openalex.org/W2413434488","https://openalex.org/W2528350688","https://openalex.org/W7225197271","https://openalex.org/W7225144778","https://openalex.org/W2807836814","https://openalex.org/W7225158175"],"abstract_inverted_index":{"Background":[0],"Metastatic":[1],"colorectal":[2],"cancer":[3,7,76,409],"(mCRC)":[4],"and":[5,15,39,80,100,135,142,151,160,188,193,243,272,325,331,338,401,411,437],"pancreatic":[6],"(mPC)":[8],"demonstrate":[9],"5-year":[10],"survival":[11,318,340],"rates":[12],"of":[13,149,178,309,328],"14%":[14],"3%,":[16],"respectively,":[17],"with":[18,184,204,229,311,424],"over":[19],"70%":[20],"patients":[21],"developing":[22],"distant":[23],"metastases":[24],"in":[25,35,47,63,75,103,124,127,132,200,247,323,345,367,408,439],"the":[26,117,307,326,388],"liver.":[27],"Immune":[28],"checkpoint":[29,377],"inhibitors":[30],"(ICIs)":[31],"exhibit":[32],"significant":[33],"efficacy":[34,123,197],"some":[36],"solid":[37],"tumors":[38,136,256],"MSI":[40,180],"CRC":[41],"but":[42],"have":[43],"limited":[44,389],"therapeutic":[45],"benefit":[46],"MSS":[48,128,182],"mCRC/mPC.":[49,64],"This":[50],"project":[51],"aims":[52],"to":[53,59,226,320,334,342,353,376,383,394,447],"identify":[54,358],"potential":[55],"novel":[56,360],"combination":[57,308,327],"strategies":[58],"overcome":[60],"ICIs":[61],"resistance":[62],"We":[65,90,357,396,415],"previously":[66],"discovered":[67],"that":[68,93,218,292,364],"liver":[69,170,253,369],"endothelial":[70],"cells":[71,77,134],"activate":[72],"HER3":[73,118,150,205,208,230,236,293,329],"signaling":[74,96],"through":[78],"NRG1":[79],"LRG1":[81],"ligands,":[82],"promoting":[83],"metastatic":[84],"growth":[85],"via":[86],"distinct":[87],"AKT/RSK":[88],"pathways.":[89],"subsequently":[91],"found":[92],"this":[94,112,233,372],"HER3-mediated":[95],"promotes":[97,365],"metabolic":[98,153,234,362],"reprogramming":[99],"lactate":[101,107,245],"production":[102],"CRC/PC":[104,133,169,248,252,303,368],"cells.":[105,249,304],"Since":[106],"impairs":[108],"T":[109,185,263,275,298,434],"cell":[110,186,264,276,299,435],"function,":[111],"study":[113],"investigates":[114],"whether":[115],"inhibiting":[116],"pathway":[119,373],"can":[120],"enhance":[121],"immunotherapy":[122,385,448],"mCRC/mPC,":[125],"especially":[126],"tumors.Methods":[129],"Metabolic":[130],"changes":[131],"were":[137,155,173],"first":[138],"determined":[139,267,279],"by":[140,157,175,191,268,280],"LC-MS":[141,215],"ELISA":[143],"for":[144,405,421],"key":[145],"metabolites.":[146],"Phosphorylation":[147],"activation":[148,237],"downstream":[152],"enzymes":[154],"evaluated":[156],"Western":[158],"blotting":[159],"IHC":[161,192],"staining":[162],"using":[163],"murine/patient":[164],"tumor":[165],"tissues.":[166],"Syngeneic":[167],"orthotopic":[168],"metastasis":[171],"models":[172,202],"established":[174],"hepatic":[176],"injection":[177],"murine":[179,251],"or":[181,210],"cells,":[183],"infiltration":[187],"function":[189,438],"assessed":[190,199],"flow":[194,412,425],"cytometry.":[195],"Therapeutic":[196],"was":[198],"these":[201],"treated":[203],"inhibition":[206,231,294,431,444],"(":[207],"KO":[209,330],"sapitinib)":[211],"and/or":[212],"anti-PD-1":[213,312,332],"antibodies.Results":[214],"analysis":[216],"revealed":[217],"mCRC/mPC":[219,375,446],"exhibited":[220],"significantly":[221],"elevated":[222],"glycolytic":[223],"metabolites":[224],"compared":[225],"primary":[227],"tumors,":[228],"reversing":[232],"reprogramming.":[235],"enhanced":[238,295],"phosphofructokinase":[239],"2":[240],"(PFK2)-S483":[241],"phosphorylation":[242],"increased":[244,273,281],"secretion":[246],"In":[250,287],"metastases,":[254],"HER3-inhibited":[255],"showed":[257],"decreased":[258,269],"lactate,":[259],"which":[260,349],"reduced":[261],"CD8+":[262,274,433],"exhaustion,":[265],"as":[266,278],"TOX":[270],"expression,":[271],"cytotoxicity,":[277],"Granzyme":[282],"B":[283],"levels":[284],"(figure":[285,355],"1).":[286],"vitro":[288],"co-culture":[289],"assays":[290],"confirmed":[291],"CD8":[296],"+":[297],"cytotoxicity":[300],"against":[301],"both":[302],"Most":[305],"importantly,":[306],"sapitinib":[310],"achieved":[313],"~40%":[314],"(2/5":[315],"mice)":[316],"tumor-free":[317,339],"up":[319,341],"140":[321],"days":[322,344],"mCRC,":[324],"led":[333],"100%":[335],"complete":[336],"response":[337],"180":[343],"mPC":[346],"(5/5":[347],"mice),":[348],"is":[350],"markedly":[351],"superior":[352],"monotherapies":[354],"2).Conclusions":[356],"a":[359,380],"HER3-PFK2-lactate":[361],"axis":[363],"immunosuppression":[366],"metastases.":[370],"Targeting":[371],"sensitizes":[374,445],"blockade,":[378],"offering":[379],"promising":[381],"strategy":[382],"extend":[384],"benefits":[386],"beyond":[387],"patient":[390],"population":[391],"currently":[392],"responsive":[393],"ICIs.Acknowledgements":[395],"thank":[397,417],"Dr.":[398,402,418],"David":[399],"Wald":[400],"Rebecca":[403],"Obeng":[404],"their":[406],"expertise":[407],"immunology":[410],"cytometry":[413,426],"support.":[414],"also":[416],"Obeng\u2019s":[419],"lab":[420],"technical":[422],"assistance":[423],"experiments.Abstract":[427],"1105":[428,441],"Figure":[429,442],"1HER3":[430],"remodels":[432],"differentiation":[436],"mPCAbstract":[440],"2HER3":[443]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-11-04T00:00:00"}
