ArticlePLoS genetics2014
Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 3 of them syntheses that pooled it.
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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.
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.
Who cites it
187 citing papers in PubMed, 3 syntheses or guidelines pooled it, 337 citations in OpenAlex.
- Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review.Asian Pacific journal of cancer prevention : APJCP · 2023Pooled it
- Therapy for advanced cholangiocarcinoma: Current knowledge and future potential.Journal of cellular and molecular medicine · 2021Pooled it
- Genomics of gallbladder cancer: the case for biomarker-driven clinical trial design.Cancer metastasis reviews · 2016Pooled it
- Trial
- Pemigatinib in previously treated Chinese patients with locally advanced or metastatic cholangiocarcinoma carrying FGFR2 fusions or rearrangements: A phase II study.Cancer medicine · 2023Trial
- A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma.Investigational new drugs · 2022Trial
- A multi-institutional phase 2 trial of regorafenib in refractory advanced biliary tract cancer.Cancer · 2020Trial
- The Diagnostic Yield of Malignancy Comparing Cytology, FISH, and Molecular Analysis of Cell Free Cytology Brush Supernatant in Patients With Biliary Strictures Undergoing Endoscopic Retrograde Cholangiography (ERC): A Prospective Study.Journal of clinical gastroenterology · 2019Trial
- Trial
- Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma.British journal of cancer · 2019Trial
- A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.Oncotarget · 2017Trial
- Multiomics combined with machine learning defines unique molecular subtypes of cholangiocarcinoma and identifies TNK1 as a therapeutic target.Hepatology (Baltimore, Md.) · 2026Article
- Global patterns of mutational profiles in biliary tract cancer.Journal of hepatology · 2026Article
- Role of the stromal and immune microenvironment in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2026Review
- ErbB Receptor Feedback Inhibitor 1 Mutation in Biliary Tract Cancers: Turning Resistance Into Response.JCO precision oncology · 2026Article
- Review
- FGFR2-Rearranged Biliary Tract Cancer: Biology, Resistance Mechanisms, and Emerging Therapeutic Strategies.Cancers · 2026Review
- Salvage resection for FGFR2 fusion-positive intrahepatic cholangiocarcinoma after pemigatinib therapy: a case report and literature review.Frontiers in oncology · 2026Article
- Advancing systemic therapy for biliary tract cancer: current strategies and emerging paradigms.Frontiers in oncology · 2026Review
- Frequent EPHA2 receptor mutations in cholangiocarcinoma disrupt receptor forward signaling supporting a tumor suppressor role.Biochimica et biophysica acta. Molecular cell research · 2026Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
49 authors at 4 institutions in 1 country.
Funding
Abstract
Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.
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Registered trials
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.