{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chaturantabut S"],"funding":["US Department of Defense, Health Program Congressionally Directed Medical Research Programs","the Cholangiocarcinoma Foundation","US Department of Defense, Health Program Congressionally Directed Medical Research Programs (CDMRP), Peer Reviewed Cancer Research Program Translational Team Science Award","National Cancer Institute","NCI NIH HHS"],"pagination":["e182417"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11996885"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["135(8)"],"pubmed_abstract":["Translocations involving FGFR2 gene fusions are common in cholangiocarcinoma and predict response to FGFR kinase inhibitors. However, response rates and durability are limited due to the emergence of resistance, typically involving FGFR2 kinase domain mutations, and to suboptimal dosing, relating to drug adverse effects. Here, we develop biparatopic antibodies targeting the FGFR2 extracellular domain (ECD) as candidate therapeutics. Biparatopic antibodies can overcome drawbacks of bivalent monospecific antibodies, which often show poor inhibitory or even agonist activity against oncogenic receptors. We show that oncogenic transformation by FGFR2 fusions requires an intact ECD. Moreover, by systematically generating biparatopic antibodies targeting distinct epitope pairs in FGFR2 ECD, we id"],"journal":["The Journal of clinical investigation"],"pubmed_title":["Identification of potent biparatopic antibodies targeting FGFR2 fusion-driven cholangiocarcinoma."],"pmcid":["PMC11996885"],"funding_grant_id":["R01 CA233626","R01 CA294689","R01CA233626","W81XWH-21-PRCRP-TTS","Andrea Lynn Scott Memorial Research Fellowship","W81XWH-20-1-0325","P50 CA127003"],"pubmed_authors":["Rodriguez DJ","Kesar D","Robinson FP","Chang L","Sellers WR","Kim JJ","Tseng YY","Dzvurumi R","Chaturantabut S","Chang YC","Oliver S","He Y","Bardeesy N","Atari A","Sinopoli A","Frederick DT","Song TY","Ching M"],"additional_accession":[]},"is_claimable":false,"name":"Identification of potent biparatopic antibodies targeting FGFR2 fusion-driven cholangiocarcinoma.","description":"Translocations involving FGFR2 gene fusions are common in cholangiocarcinoma and predict response to FGFR kinase inhibitors. However, response rates and durability are limited due to the emergence of resistance, typically involving FGFR2 kinase domain mutations, and to suboptimal dosing, relating to drug adverse effects. Here, we develop biparatopic antibodies targeting the FGFR2 extracellular domain (ECD) as candidate therapeutics. Biparatopic antibodies can overcome drawbacks of bivalent monospecific antibodies, which often show poor inhibitory or even agonist activity against oncogenic receptors. We show that oncogenic transformation by FGFR2 fusions requires an intact ECD. Moreover, by systematically generating biparatopic antibodies targeting distinct epitope pairs in FGFR2 ECD, we id","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-06-01T10:45:02.51Z","creation":"2026-04-08T11:40:17.262Z"},"accession":"S-EPMC11996885","cross_references":{"pubmed":["40014401"],"doi":["10.1172/JCI182417"]}}