Evidence map›Paper›PMID 40014401›Full record

ArticleThe Journal of clinical investigation2025

Identification of potent biparatopic antibodies targeting FGFR2 fusion-driven cholangiocarcinoma.

Saireudee Chaturantabut, Sydney Oliver, Dennie T Frederick, Jiwan J Kim, Foxy P Robinson, Alessandro Sinopoli, Tian-Yu Song, Yao He, Yuan-Chen Chang, Diego J Rodriguez and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Saireudee ChaturantabutBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Sydney OliverBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Dennie T FrederickBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Jiwan J KimBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Foxy P RobinsonBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Alessandro SinopoliRidgeline Discovery GmbH, Basel, Switzerland.
Tian-Yu SongBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Yao HeBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Yuan-Chen ChangBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Diego J RodriguezBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Liang ChangBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Devishi KesarBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Meilani ChingBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Ruvimbo DzvurumiBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Adel AtariBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Yuen-Yi TsengBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Nabeel BardeesyBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
William R SellersBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI SHIVDASANI, RAMESH A · 2007 to 2023
$33.2M
The function of the PRMT5 methylosome in MTAP deleted cancersR01CA233626 · NCI · BROAD INSTITUTE, INC. · PI Andrew James Aguirre, WILLIAM R SELLERS · 2019 to 2026
$2.9M
Targeting FGFR Alterations in Gastroesophageal CancerR01CA294689 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI NABEEL El-BARDEESY, Sandra Ryeom · 2024 to 2026
$2.1M
NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA233626NCI NIH HHS R01 CA294689
6 · The paper itself

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 identified antibodies that effectively block signaling and malignant growth driven by FGFR2 fusions. Importantly, these antibodies demonstrate efficacy in vivo, synergy with FGFR inhibitors, and activity against FGFR2 fusions harboring kinase domain mutations. Thus, we believe that biparatopic antibodies may serve as an innovative treatment option for patients with FGFR2-altered cholangiocarcinoma.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaOncogene Proteins, FusionReceptor, Fibroblast Growth Factor, Type 2AnimalsCell Line, TumorHumansMiceFGFR2 protein, humanOncogene Proteins, FusionReceptor, Fibroblast Growth Factor, Type 2Drug therapyLiver cancerOncologySignal transductionTherapeutics

Identifiers

PMID40014401
PMCPMC11996885

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.