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FGFR-Altered Cholangiocarcinoma

FGFR‑Altered Cholangiocarcinoma (FGFR2 fusion/rearranged iCCA) — Disease Characteristics Research Report

2026-04-05
Falcon MONDO:0003210 Model: Edison Scientific Literature 33 citations

FGFR‑Altered Cholangiocarcinoma (FGFR2 fusion/rearranged iCCA) — Disease Characteristics Research Report

Target Disease

1. Disease Information

1.1 Concise overview (definition)

Cholangiocarcinoma (CCA) is a malignant tumor of the biliary epithelium and is commonly classified anatomically into intrahepatic (iCCA), perihilar, and extrahepatic forms (patel2023fdaapprovalsummary pages 1-3). The most clinically actionable FGFR‑altered form is FGFR2 fusion/rearrangement–positive iCCA, in which oncogenic FGFR2 gene fusions/rearrangements (structural variants) define a molecular subtype that can be treated with FGFR tyrosine kinase inhibitors (TKIs) (patel2023fdaapprovalsummary pages 1-3, gonzalezmedina2024clinicalvalueof pages 1-2).

1.2 Key identifiers and synonyms

1.3 Evidence source types

Most knowledge for “FGFR‑altered CCA” is derived from aggregated disease‑level resources (clinical trials, cohort studies, guidelines, and translational studies), not single‑patient EHRs; exceptions include case reports (not emphasized here) and small observational cohorts (gonzalezmedina2024clinicalvalueof pages 1-2, kim2024burdenofmortality pages 1-3).

2. Etiology

2.1 Disease causal factors (mechanistic)

FGFR2 fusion/rearrangement in iCCA is best conceptualized as an oncogenic driver alteration that results in ligand‑independent FGFR signaling and downstream proliferative/survival pathway activation (MAPK and PI3K axis), creating a therapeutically targetable dependency (xin2026fgfr2rearrangedbiliarytract pages 8-10, diperi2024convergentmapkpathway pages 1-3).

2.2 Risk factors (for cholangiocarcinoma overall)

Many established CCA risk factors reflect chronic biliary inflammation, biliary obstruction, chronic liver disease, infections, and carcinogenic exposures.

Authoritative guideline summary (BSG Gut 2024; published Sep 2024): - The guideline provides effect estimates for multiple exposures, including very high relative risks for choledochal cysts and choledocholithiasis, elevated risks for cirrhosis, and increased odds for liver fluke infection (Opisthorchis viverrini/Clonorchis spp.) (rushbrook2024britishsocietyof pages 5-5). - Example values explicitly stated in the guideline excerpt include: - Choledochal cyst: meta‑analysis RR 26.7 (and another estimate 34.9 in the same table) (rushbrook2024britishsocietyof pages 5-5). - Choledocholithiasis: meta‑analysis RR 10.1 (and another estimate 18.6) (rushbrook2024britishsocietyof pages 5-5). - Cirrhosis: meta‑analysis RR 15.3 (additional estimate 3.8) (rushbrook2024britishsocietyof pages 5-5). - Thorotrast exposure: retrospective study RR >300 (rushbrook2024britishsocietyof pages 5-5).

Review summary (Current Oncology 2024; published Jun 2024): A BTC review lists major risk factors as “cholelithiasis, biliary flukes in Asia, chronic inflammatory diseases of the bile ducts, metabolic syndrome-associated liver diseases… tobacco use, chronic hepatitis B and C infections, and cirrhosis” (rosbuxo2024integratingmolecularinsights pages 1-2).

2.3 Protective factors

No validated protective genetic variants or definitive environmental protective factors specific to FGFR‑altered iCCA were identified in the retrieved sources. Prevention is therefore largely addressed as risk‑factor reduction for biliary tract cancers broadly (e.g., metabolic risk) (su2024globalregionaland pages 1-2).

2.4 Gene–environment interactions

Direct gene–environment interaction evidence specific to FGFR2 fusion iCCA was not identified in the retrieved 2023–2024 sources. Etiology‑stratified genomic reviews suggest that molecular landscapes vary by etiologic background (e.g., fluke‑associated vs non‑fluke CCA) (oura2025chronicliverdisease pages 13-14).

3. Phenotypes

3.1 Core clinical phenotype (CCA/iCCA)

Clinical presentation is often nonspecific and many patients present with advanced disease (rosbuxo2024integratingmolecularinsights pages 1-2, patel2023fdaapprovalsummary pages 1-3). The FGFR2‑fusion iCCA subgroup is clinically important primarily because it predicts benefit from FGFR inhibition rather than because it has unique pathognomonic symptoms.

3.2 Suggested phenotype list with HPO mapping (knowledge‑base oriented)

(Phenotypes below reflect common CCA clinical manifestations and treatment‑related effects; frequencies were not consistently provided in retrieved sources.)

Tumor/location related - Abdominal pain — HP:0002027 - Jaundice — HP:0000952 (more typical for extrahepatic obstruction; may occur in iCCA with biliary obstruction) - Weight loss — HP:0001824 - Fatigue — HP:0012378

Laboratory abnormalities (often used clinically) - Elevated alkaline phosphatase — HP:0003155 - Elevated gamma‑glutamyltransferase — HP:0003285 (and was lower in FGFR2‑fusion cases in one surgical cohort) (liu2024fgfr2fusionrearrangementis pages 1-2) - CA19‑9 elevation — HP:0040217 (common in BTC care pathways; not quantified in retrieved evidence)

Targeted therapy adverse events (FGFR inhibitors) - Hyperphosphatemia — HP:0002905 (explicitly a common AE and key risk for pemigatinib) (patel2023fdaapprovalsummary pages 1-3, patel2023fdaapprovalsummary pages 3-5) - Dry eye / ocular toxicity — HP:0001097 / (ocular AE category) (patel2023fdaapprovalsummary pages 1-3, patel2023fdaapprovalsummary pages 3-5) - Alopecia — HP:0001596 (listed among common pemigatinib adverse reactions) (patel2023fdaapprovalsummary pages 1-3)

3.3 Quality‑of‑life impact

The retrieved 2023–2024 sources did not provide standardized QoL instrument outcomes (EQ‑5D, SF‑36, PROMIS) specific to FGFR‑altered iCCA.

4. Genetic / Molecular Information

4.1 Causal/driver genes and alteration classes

4.2 Frequency / prevalence of FGFR2 fusions in iCCA

4.3 Example fusion partners (and implications)

In FIGHT‑202 Cohort A, FGFR2‑BICC1 was the most common in‑frame fusion (34% of in‑frame fusions) (patel2023fdaapprovalsummary pages 3-5). A broader basket‑trial synthesis similarly highlights BICC1 among common partners (erul2026fibroblastgrowthfactor pages 4-6).

4.4 Somatic vs germline

FGFR2 fusions/rearrangements described here are somatic tumor alterations detected by tumor testing (tissue and/or plasma) (gonzalezmedina2024clinicalvalueof pages 1-2, patel2023fdaapprovalsummary pages 3-5).

4.5 Modifier/co‑alterations influencing response/resistance

Evidence indicates resistance can involve both on‑target FGFR2 kinase‑domain mutations and off‑target bypass alterations (MAPK; PI3K/mTOR) detected by serial tissue/ctDNA sequencing (facchinetti2024understandingandovercoming pages 1-2, diperi2024convergentmapkpathway pages 1-3).

5. Environmental Information

No environmental causes are known to specifically predispose to acquisition of FGFR2 fusions, but environmental and infectious exposures contribute to cholangiocarcinoma risk overall (e.g., liver flukes, carcinogenic exposures, metabolic risk), as summarized in guidelines and global burden analyses (rushbrook2024britishsocietyof pages 5-5, su2024globalregionaland pages 1-2).

6. Mechanism / Pathophysiology

6.1 Core pathway biology (FGFR2 fusion oncogenic signaling)

FGFR2 fusions function as actionable oncogenic drivers, and FGFR signaling interfaces strongly with canonical proliferative and survival pathways. - Translational resistance studies and reviews explicitly implicate MAPK signaling and PI3K/AKT/mTOR as key downstream pathways relevant to resistance and bypass signaling (diperi2024convergentmapkpathway pages 1-3, diperi2024convergentmapkpathway pages 3-5).

Suggested GO Biological Process terms (for annotation): - MAPK cascade — GO:0000165 - PI3K/AKT signaling — GO:0014065 (phosphatidylinositol 3‑kinase signaling) - Positive regulation of cell proliferation — GO:0008284 - Receptor tyrosine kinase signaling — GO:0007169

6.2 Acquired resistance mechanisms (2024–2025 high‑impact evidence)

6.2.1 MAPK pathway convergence (Journal of Hepatology 2024)

A key 2024 mechanistic paper concludes that acquired resistance commonly converges on MAPK re‑activation and/or new FGFR2 mutations. - In a cohort with repeat sequencing (n=17), 11/17 (64.7%) developed new FGFR2 mutations and 9/17 (52.9%) developed new MAPK pathway alterations, with 7 acquiring both (diperi2024convergentmapkpathway pages 1-3). - Longitudinal ctDNA detected emergent MAPK alterations including BRAF V600E and multiple RAS variants in an example patient (diperi2024convergentmapkpathway pages 1-3).

6.2.2 Polyclonal on‑target FGFR2 kinase domain mutations (Clinical Cancer Research 2024)

A prospective resistance program across FGFR2‑driven tumors found polyclonal FGFR2 kinase‑domain mutations are particularly frequent in cholangiocarcinoma. - “Polyclonal FGFR2 kinase domain mutations were frequent” in cholangiocarcinoma (14/27 patients) (facchinetti2024understandingandovercoming pages 1-2). - The study reports distinct patterns by inhibitor class: at resistance to reversible inhibitors many residues can be mutated; after futibatinib resistance was restricted to fewer hotspots including the molecular brake N550 and gatekeeper V565 (facchinetti2024understandingandovercoming pages 1-2).

6.2.3 Specific acquired resistance residues (functional/preclinical evidence)

  • A 2024 preclinical study of an FGFR inhibitor (tasurgratinib) highlights N549H/K as “major acquired mutations in CCA” and demonstrates potency against these in cell models and PDX (kawano2024antitumoractivityof pages 1-2).

6.3 Cell types and microenvironment

A surgical cohort study suggests FGFR2 fusion/rearrangement can associate with an “immune‑activated” state (lower Tregs and N2 neutrophils, higher N1 neutrophils), supporting prognostic stratification and potential immunotherapy targeting hypotheses (liu2024fgfr2fusionrearrangementis pages 1-2).

Suggested Cell Ontology (CL) terms (for annotation): - Cholangiocyte — CL:1000427 (primary malignant lineage) - Regulatory T cell — CL:0000815 (Treg) - Neutrophil — CL:0000775

7. Anatomical Structures Affected

7.1 Organ and system level

Suggested UBERON terms (for annotation): - Liver — UBERON:0002107 - Intrahepatic bile duct — UBERON:0003706 - Biliary tract — UBERON:0000059

7.2 Tissue/cellular level

7.3 Subcellular level

8. Temporal Development

8.1 Onset

Typically adult/older adult onset for cholangiocarcinoma overall; guideline excerpt reports median age at diagnosis 75 (population‑level CCA context) (rushbrook2024britishsocietyof pages 5-5).

8.2 Progression

Advanced/metastatic disease at presentation is common and drives reliance on systemic therapy (rosbuxo2024integratingmolecularinsights pages 1-2). FGFR inhibitor benefit is meaningful but limited by acquired resistance, often within months (e.g., resistance observed as progression under therapy with emergent mutations detectable in ctDNA) (gonzalezmedina2024clinicalvalueof pages 1-2, diperi2024convergentmapkpathway pages 1-3).

9. Inheritance and Population

9.1 Inheritance

FGFR2 fusions/rearrangements in iCCA are somatic cancer alterations, not inherited Mendelian disorders (patel2023fdaapprovalsummary pages 3-5).

9.2 Epidemiology (recent quantitative data)

Because “FGFR‑altered cholangiocarcinoma” is molecularly defined, population incidence is usually inferred as iCCA incidence × FGFR2 fusion prevalence. Recent epidemiology sources are mostly for BTC/CCA overall.

US mortality trends (2018–2023; Clinical and Molecular Hepatology 2024, published Oct 2024): - Intrahepatic cholangiocarcinoma mortality increased with APC 3.1% (95% CI 1.2–4.9%) (kim2024burdenofmortality pages 1-3).

Global burden patterns (GBD 2019 analysis; Frontiers in Medicine 2024, published Apr 2024): - From 1990 to 2019, incident cases increased 1.85‑fold and deaths 1.82‑fold, while age‑standardized rates generally decreased (su2024globalregionaland pages 1-2). - High BMI was identified as a leading attributable risk factor, accounting for 15.2% of deaths and 15.7% of DALYs globally in 2019 (su2024globalregionaland pages 1-2).

10. Diagnostics

10.1 Molecular diagnostics are essential (FGFR2)

A key operational requirement in FGFR‑altered iCCA is robust molecular testing to identify FGFR2 fusions.

Regulatory companion diagnostic: The FDA approval summary for pemigatinib states FDA “also approved the FoundationOne CDX… as a companion diagnostic for patient selection” (patel2023fdaapprovalsummary pages 1-3).

10.2 Tissue testing (standard of care)

FIGHT‑202 defined eligibility by presence of “FGFR2 fusion or other rearrangement… as detected by an FDA‑approved test” (patel2023fdaapprovalsummary pages 1-3). Practical implication: tissue NGS (DNA and/or RNA fusion detection) is commonly used, with attention to tissue stewardship.

10.3 Liquid biopsy / ctDNA (2024 development)

A major 2024 study in Clinical Cancer Research evaluated plasma detection and longitudinal monitoring: - Quote (Purpose): “FGFR2 fusions occur in 10% to 15% of patients with intrahepatic cholangiocarcinoma (iCCA)…” (gonzalezmedina2024clinicalvalueof pages 1-2). - Detection performance: 16/18 patients (88.9%) had FGFR2 fusion events detectable in plasma (gonzalezmedina2024clinicalvalueof pages 1-2). - Clinical management utility: increased ctDNA or emerging resistance mutations enabled “earlier detection of disease progression compared with standard radiologic imaging methods” (gonzalezmedina2024clinicalvalueof pages 1-2).

Implementation interpretation: Plasma ctDNA can complement tissue testing, especially for monitoring resistance evolution and anticipating progression, but tissue remains important for initial diagnosis and comprehensive profiling (gonzalezmedina2024clinicalvalueof pages 1-2, diperi2024convergentmapkpathway pages 1-3).

10.4 Imaging and pathology (CCA general)

Detailed imaging algorithms were not extracted in the evidence snippets used here; however, CCA diagnosis generally requires radiologic and histopathologic confirmation, and is addressed in major guidelines (rushbrook2024britishsocietyof pages 5-5).

11. Outcome / Prognosis

11.1 General BTC/CCA prognosis (population context)

A 2024 precision management review reports poor relative survival in BTC: “1, 3, and 5 years post‑diagnosis estimated at 25%, 10%, and 7%, respectively” (rosbuxo2024integratingmolecularinsights pages 1-2). The same review states: “Approximately 65% of patients receive only the best supportive care at the time of diagnosis” (rosbuxo2024integratingmolecularinsights pages 1-2).

11.2 Prognosis associated with FGFR2 fusion/rearrangement (surgical cohort)

A 2024 surgical cohort study reports FGFR2 fusion/rearrangement as an “independent protective factor” for overall and relapse‑free survival and associates it with an immune‑activated microenvironment (liu2024fgfr2fusionrearrangementis pages 1-2).

12. Treatment

12.1 Targeted FGFR inhibition (core application)

Two FDA‑approved FGFR inhibitors—pemigatinib and futibatinib—are central real‑world implementations for previously treated advanced FGFR2 fusion/rearranged cholangiocarcinoma (patel2023fdaapprovalsummary pages 1-3, gonzalezmedina2024clinicalvalueof pages 1-2).

Table (click to expand)
Therapy (drug; reversible vs irreversible) Target/eligible alteration Trial (name; NCT) Setting/line Key efficacy Key safety signals Regulatory/implementation note
Pemigatinib; selective FGFR1–3, reversible/ATP-competitive Unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or other rearrangement; Cohort A included 107 patients, 98% with iCCA; FGFR2-BICC1 was the most common in-frame fusion partner (34%) FIGHT-202; NCT02924376 Previously treated; disease progressed on or after ≥1 prior therapy ORR 35.5% (95% CI 26.5–45.3%); 3 CRs (2.8%) and 35 PRs (32.7%); median DOR 9.1 months (95% CI 6.0–13.5); 63% of responders had DOR ≥6 months and 18% ≥12 months. FDA summary also reports ORR 36% (95% CI 27–45) and median DOR 9.1 months; later update reported median PFS 7.0 months and OS 17.5 months (patel2023fdaapprovalsummary pages 3-5, patel2023fdaapprovalsummary pages 1-3, erul2026fibroblastgrowthfactor pages 4-6) Hyperphosphatemia was a key/common AE; ocular toxicity was an important risk; common ocular events included dry eye. In 146 treated CCA patients, 99% had ≥1 AE, grade 3–4 ADRs occurred in 64%, fatal adverse reactions in 4.1% (patel2023fdaapprovalsummary pages 1-3, patel2023fdaapprovalsummary pages 3-5, erul2026fibroblastgrowthfactor pages 4-6) FDA accelerated approval: 2020-04-17 for adults with previously treated unresectable locally advanced or metastatic CCA with FGFR2 fusion/rearrangement. FoundationOne CDX approved as companion diagnostic (patel2023fdaapprovalsummary pages 1-3)
Futibatinib; pan-FGFR1–4, irreversible/covalent Previously treated unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma with FGFR2 gene fusions or other rearrangements FOENIX-CCA2; NCT not provided in available context Previously treated; unresectable locally advanced or metastatic iCCA ORR 42% (95% CI 32–52%); reported median PFS ~9.0 months and median OS 21.7 months in review synthesis of phase II data (crolley2024…locally pages 2-3, xin2026fgfr2rearrangedbiliarytract pages 5-6) Hyperphosphatemia reported among the most common treatment-emergent adverse events; ocular toxicity not explicitly quantified in available context (xin2026fgfr2rearrangedbiliarytract pages 5-6) Received regulatory approval based on FOENIX-CCA2 phase II data; implementation note in available context emphasizes use in previously treated FGFR2-rearranged iCCA and potential activity after resistance to reversible FGFR inhibitors, but no companion diagnostic was specified in the available context (crolley2024…locally pages 2-3, gonzalezmedina2024clinicalvalueof pages 1-2)

Table: This table summarizes the core clinical evidence for the two leading FGFR-targeted therapies used in FGFR-altered cholangiocarcinoma, focusing on pivotal trial outcomes, safety, and implementation details. It is useful for quickly comparing pemigatinib and futibatinib in the molecularly defined FGFR2-rearranged setting.

12.1.1 Pemigatinib (PEMAZYRE) — pivotal evidence

FDA accelerated approval language (Clinical Cancer Research 2023; published Oct 2023): - Quote: “On April 17, 2020, the FDA granted accelerated approval to pemigatinib… for… cholangiocarcinoma with an FGFR2 fusion or other rearrangement…” (patel2023fdaapprovalsummary pages 1-3). - Efficacy basis: ORR 36% (95% CI 27–45); median DOR 9.1 months (patel2023fdaapprovalsummary pages 1-3). A detailed breakdown reports ORR 35.5% with 2.8% CR and median DOR 9.1 months (patel2023fdaapprovalsummary pages 3-5). - Key toxicities: hyperphosphatemia and ocular toxicity highlighted as important risks (patel2023fdaapprovalsummary pages 1-3, patel2023fdaapprovalsummary pages 3-5).

Suggested MAXO terms: - FGFR inhibitor therapy — MAXO:0000758 (term name may vary by implementation; use as a targeted small‑molecule therapy action) - Molecular targeted therapy — MAXO:0000010

12.1.2 Futibatinib (LYTGOBI) — pivotal evidence synthesis

A 2026 synthesis reports FOENIX‑CCA2 outcomes (used here only for quantitative endpoints): ORR 42%, median PFS 9.0 months, median OS 21.7 months (xin2026fgfr2rearrangedbiliarytract pages 5-6). A 2024 review excerpt also reports FOENIX‑CCA2 ORR 42% (95% CI 32–52%) (crolley2024…locally pages 2-3).

Clinical positioning and sequencing: A 2024 liquid biopsy study notes futibatinib “has shown to be effective in some patients with acquired resistance to other FGFRi” (gonzalezmedina2024clinicalvalueof pages 1-2), consistent with the mechanistic rationale that irreversible inhibitors may retain activity against subsets of resistance mutations (facchinetti2024understandingandovercoming pages 1-2).

12.2 Managing and anticipating resistance (current expert analysis)

A 2024 resistance program supports a sequential, molecularly guided strategy: - Polyclonal FGFR2 kinase‑domain mutations are common in cholangiocarcinoma (14/27), and off‑target MAPK/PI3K alterations can co‑occur (facchinetti2024understandingandovercoming pages 1-2). - Longitudinal ctDNA and/or re‑biopsy can inform whether switching to an irreversible inhibitor is plausible, or whether bypass pathway inhibition (e.g., PI3K/mTOR) is rational in a subset (e.g., everolimus benefit in selected cases) (facchinetti2024understandingandovercoming pages 1-2).

12.3 Combination strategies (research frontier)

Preclinical and translational evidence indicates MAPK pathway co‑activation can drive resistance and that MEK inhibition can be synergistic with FGFR inhibition in vitro, though not universally effective (diperi2024convergentmapkpathway pages 1-3).

12.4 Ongoing / recent clinical trials (ClinicalTrials.gov; selected)

(Representative examples from retrieved trials list) - FIGHT‑202 (pemigatinib): NCT02924376 — completed (patel2023fdaapprovalsummary pages 1-3). - Infigratinib phase 3 first‑line iCCA with FGFR2 fusions: NCT03773302 — terminated (trial registry evidence retrieved). - Futibatinib advanced CCA with FGFR2 fusion/rearrangement: NCT05727176 — recruiting phase 2 (trial registry evidence retrieved).

13. Prevention

13.1 Primary prevention (BTC/CCA context)

Global burden analysis identifies high BMI as a major attributable risk factor for gallbladder and biliary tract cancers (15.2% of deaths; 15.7% DALYs in 2019), supporting metabolic risk reduction as a plausible population‑level prevention strategy (su2024globalregionaland pages 1-2).

13.2 Secondary prevention / screening

Specific screening recommendations for FGFR‑altered iCCA were not identified in the retrieved evidence excerpts. For CCA broadly, guideline efforts focus on risk factor identification and diagnostic pathways (rushbrook2024britishsocietyof pages 5-5).

14. Other Species / Natural Disease

No naturally occurring non‑human species entity specifically corresponding to “FGFR2 fusion iCCA” was identified from the retrieved sources. This section remains not well characterized in the current evidence set.

15. Model Organisms / Experimental Models

15.1 Preclinical resistance modeling and translational platforms (2024)

Multiple model classes are actively used to study FGFR2 fusion iCCA biology and resistance.

Suggested model‑related ontology hooks: - Patient‑derived xenograft model (PDX) — model type annotation - Organoid model — not directly evidenced in the extracted snippets for FGFR2 fusion iCCA here; however, organoids are broadly discussed as relevant CCA preclinical systems in recent methodological reviews (not used as primary evidence in this report).

Expert Synthesis (2023–2024 emphasis)

  1. FGFR2 fusions/rearrangements are frequent (≈10–15%) and largely iCCA‑restricted, providing a clear precision‑oncology target with FDA‑approved therapies (pemigatinib; futibatinib) (patel2023fdaapprovalsummary pages 1-3, gonzalezmedina2024clinicalvalueof pages 1-2, liu2024fgfr2fusionrearrangementis pages 1-2).
  2. Clinical benefit is substantial but time‑limited, with pemigatinib ORR ~36% and median DOR ~9 months in the pivotal accelerated‑approval dataset (patel2023fdaapprovalsummary pages 1-3, patel2023fdaapprovalsummary pages 3-5).
  3. Resistance is heterogeneous and often polyclonal, involving on‑target FGFR2 kinase‑domain mutations and bypass pathway alterations (MAPK; PI3K/mTOR), motivating serial molecular monitoring and rational sequencing/combination strategies (facchinetti2024understandingandovercoming pages 1-2, diperi2024convergentmapkpathway pages 1-3).
  4. Liquid biopsy moved from concept to clinical utility in 2024: plasma NGS detected FGFR2 fusions in 88.9% of tissue‑confirmed cases and enabled earlier progression detection than imaging in a longitudinal study, supporting real‑world implementation for monitoring (gonzalezmedina2024clinicalvalueof pages 1-2).

Key abstract quotes (verbatim) supporting major claims

  • FDA accelerated approval statement for pemigatinib: “On April 17, 2020, the FDA granted accelerated approval to pemigatinib… for… cholangiocarcinoma with an FGFR2 fusion or other rearrangement…” (Clinical Cancer Research; Oct 2023) (patel2023fdaapprovalsummary pages 1-3).
  • FGFR2 fusion prevalence and plasma detection rationale: “FGFR2 fusions occur in 10% to 15% of patients with intrahepatic cholangiocarcinoma (iCCA)…” (Clinical Cancer Research; Jul 2024) (gonzalezmedina2024clinicalvalueof pages 1-2).

URLs and publication dates (selected high‑authority sources used)

References

  1. (gonzalezmedina2024clinicalvalueof pages 1-2): Alberto González-Medina, Maria Vila-Casadesús, Marina Gomez-Rey, Carles Fabregat-Franco, Alexandre Sierra, Tian V. Tian, Florian Castet, Gloria Castillo, Judit Matito, Paola Martinez, Josep M. Miquel, Paolo Nuciforo, Raquel Pérez-López, Teresa Macarulla, and Ana Vivancos. Clinical value of liquid biopsy in patients with fgfr2 fusion–positive cholangiocarcinoma during targeted therapy. Clinical Cancer Research, 30:4491-4504, Jul 2024. URL: https://doi.org/10.1158/1078-0432.ccr-23-3780, doi:10.1158/1078-0432.ccr-23-3780. This article has 25 citations and is from a highest quality peer-reviewed journal.

  2. (patel2023fdaapprovalsummary pages 1-3): Timil H. Patel, Leigh Marcus, M. Naomi Horiba, Martha Donoghue, Somak Chatterjee, Pallavi S. Mishra-Kalyani, Robert N. Schuck, Yangbing Li, Xinyuan Zhang, Jeanne Fourie Zirkelbach, Rosane Charlab, Jiang Liu, Yuching Yang, Steven J. Lemery, Richard Pazdur, Marc R. Theoret, and Lola A. Fashoyin-Aje. Fda approval summary: pemigatinib for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with fgfr2 fusion or other rearrangement. Clinical Cancer Research, 29:838-842, Oct 2023. URL: https://doi.org/10.1158/1078-0432.ccr-22-2036, doi:10.1158/1078-0432.ccr-22-2036. This article has 65 citations and is from a highest quality peer-reviewed journal.

  3. (liu2024fgfr2fusionrearrangementis pages 1-2): Shaoqing Liu, Jialei Weng, Manqing Cao, Qiang Zhou, Minghao Xu, Wenxin Xu, Zhiqiu Hu, Minghao Xu, Qiongzhu Dong, Xia Sheng, Chenhao Zhou, and Ning Ren. Fgfr2 fusion/rearrangement is associated with favorable prognosis and immunoactivation in patients with intrahepatic cholangiocarcinoma. The Oncologist, 29:e1734-e1747, Jul 2024. URL: https://doi.org/10.1093/oncolo/oyae170, doi:10.1093/oncolo/oyae170. This article has 6 citations.

  4. (xin2026fgfr2rearrangedbiliarytract pages 5-6): Xin Xin and Ruoyu Miao. Fgfr2-rearranged biliary tract cancer: biology, resistance mechanisms, and emerging therapeutic strategies. Cancers, 18:531, Feb 2026. URL: https://doi.org/10.3390/cancers18030531, doi:10.3390/cancers18030531. This article has 0 citations.

  5. (rushbrook2024britishsocietyof pages 5-5): S. Rushbrook, Timothy J. Kendall, Yoh Zen, R. Albazaz, Prakash Manoharan, Stephen P Pereira, R. Sturgess, Brian R Davidson, Hassan Z. Malik, Derek Manas, Nigel Heaton, K. R. Prasad, John Bridgewater, Juan W Valle, Rebecca Goody, Maria A. Hawkins, Wendy Prentice, H. Morement, Martine Walmsley, Shahid A. Khan, and Hepatology Gastroenterology Section Shahid A Khan. British society of gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma. Gut, 73:16-46, Sep 2024. URL: https://doi.org/10.1136/gutjnl-2023-330029, doi:10.1136/gutjnl-2023-330029. This article has 98 citations and is from a highest quality peer-reviewed journal.

  6. (kim2024burdenofmortality pages 1-3): Donghee Kim, Richie Manikat, Karn Wijarnpreecha, George Cholankeril, and Aijaz Ahmed. Burden of mortality from hepatocellular carcinoma and biliary tract cancers by race and ethnicity and sex in us, 2018–2023. Clinical and Molecular Hepatology, 30:756-770, Oct 2024. URL: https://doi.org/10.3350/cmh.2024.0318, doi:10.3350/cmh.2024.0318. This article has 22 citations.

  7. (xin2026fgfr2rearrangedbiliarytract pages 8-10): Xin Xin and Ruoyu Miao. Fgfr2-rearranged biliary tract cancer: biology, resistance mechanisms, and emerging therapeutic strategies. Cancers, 18:531, Feb 2026. URL: https://doi.org/10.3390/cancers18030531, doi:10.3390/cancers18030531. This article has 0 citations.

  8. (diperi2024convergentmapkpathway pages 1-3): Timothy P. DiPeri, Ming Zhao, Kurt W. Evans, Kaushik Varadarajan, Tyler Moss, Stephen Scott, Michael P. Kahle, Charnel C. Byrnes, Huiqin Chen, Sunyoung S. Lee, Abdel-Baset Halim, Hiroshi Hirai, Volker Wacheck, Lawrence N. Kwong, Jordi Rodon, Milind Javle, and Funda Meric-Bernstam. Convergent mapk pathway alterations mediate acquired resistance to fgfr inhibitors in fgfr2 fusion-positive cholangiocarcinoma. Journal of Hepatology, 80:322-334, Feb 2024. URL: https://doi.org/10.1016/j.jhep.2023.10.041, doi:10.1016/j.jhep.2023.10.041. This article has 36 citations and is from a highest quality peer-reviewed journal.

  9. (rosbuxo2024integratingmolecularinsights pages 1-2): Mar Ros-Buxó, Ezequiel Mauro, Tamara Sauri, Gemma Iserte, Carla Fuster-Anglada, Alba Díaz, Laura Sererols-Viñas, Silvia Affo, and Alejandro Forner. Integrating molecular insights into biliary tract cancer management: a review of personalized therapeutic strategies. Current Oncology, 31:3615-3629, Jun 2024. URL: https://doi.org/10.3390/curroncol31070266, doi:10.3390/curroncol31070266. This article has 5 citations.

  10. (su2024globalregionaland pages 1-2): Jiao Su, Yuanhao Liang, and Xiaofeng He. Global, regional, and national burden and trends analysis of gallbladder and biliary tract cancer from 1990 to 2019 and predictions to 2030: a systematic analysis for the global burden of disease study 2019. Frontiers in Medicine, Apr 2024. URL: https://doi.org/10.3389/fmed.2024.1384314, doi:10.3389/fmed.2024.1384314. This article has 40 citations.

  11. (oura2025chronicliverdisease pages 13-14): Kyoko Oura, Asahiro Morishita, Mai Nakahara, Tomoko Tadokoro, Koji Fujita, Joji Tani, Tsutomu Masaki, and Hideki Kobara. Chronic liver disease associated cholangiocarcinoma: genomic insights and precision therapeutic strategies. Cancers, 17:3052, Sep 2025. URL: https://doi.org/10.3390/cancers17183052, doi:10.3390/cancers17183052. This article has 2 citations.

  12. (patel2023fdaapprovalsummary pages 3-5): Timil H. Patel, Leigh Marcus, M. Naomi Horiba, Martha Donoghue, Somak Chatterjee, Pallavi S. Mishra-Kalyani, Robert N. Schuck, Yangbing Li, Xinyuan Zhang, Jeanne Fourie Zirkelbach, Rosane Charlab, Jiang Liu, Yuching Yang, Steven J. Lemery, Richard Pazdur, Marc R. Theoret, and Lola A. Fashoyin-Aje. Fda approval summary: pemigatinib for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with fgfr2 fusion or other rearrangement. Clinical Cancer Research, 29:838-842, Oct 2023. URL: https://doi.org/10.1158/1078-0432.ccr-22-2036, doi:10.1158/1078-0432.ccr-22-2036. This article has 65 citations and is from a highest quality peer-reviewed journal.

  13. (erul2026fibroblastgrowthfactor pages 4-6): Enes Erul, Sergio Cifuentes-Canaval, Akhil Santhosh, Emir Sokolović, Mario Della Mura, Gerardo Cazzato, Pınar Kubilay Tolunay, and Alessandro Rizzo. Fibroblast growth factor receptor (fgfr) inhibitors for the treatment of cholangiocarcinoma: key therapeutic developments and knowledge gaps. Drug Design, Development and Therapy, Volume 20:1-21, Feb 2026. URL: https://doi.org/10.2147/dddt.s559328, doi:10.2147/dddt.s559328. This article has 0 citations.

  14. (facchinetti2024understandingandovercoming pages 1-2): Francesco Facchinetti, Yohann Loriot, Floriane Brayé, Damien Vasseur, Rastislav Bahleda, Ludovic Bigot, Rémy Barbé, Catline Nobre, David Combarel, Stefan Michiels, Antoine Italiano, Cristina Smolenschi, Lambros Tselikas, Jean-Yves Scoazec, Santiago Ponce-Aix, Benjamin Besse, Fabrice André, Ken A. Olaussen, Antoine Hollebecque, and Luc Friboulet. Understanding and overcoming resistance to selective fgfr inhibitors across fgfr2-driven malignancies. Clinical Cancer Research, 30:4943-4956, Sep 2024. URL: https://doi.org/10.1158/1078-0432.ccr-24-1834, doi:10.1158/1078-0432.ccr-24-1834. This article has 33 citations and is from a highest quality peer-reviewed journal.

  15. (diperi2024convergentmapkpathway pages 3-5): Timothy P. DiPeri, Ming Zhao, Kurt W. Evans, Kaushik Varadarajan, Tyler Moss, Stephen Scott, Michael P. Kahle, Charnel C. Byrnes, Huiqin Chen, Sunyoung S. Lee, Abdel-Baset Halim, Hiroshi Hirai, Volker Wacheck, Lawrence N. Kwong, Jordi Rodon, Milind Javle, and Funda Meric-Bernstam. Convergent mapk pathway alterations mediate acquired resistance to fgfr inhibitors in fgfr2 fusion-positive cholangiocarcinoma. Journal of Hepatology, 80:322-334, Feb 2024. URL: https://doi.org/10.1016/j.jhep.2023.10.041, doi:10.1016/j.jhep.2023.10.041. This article has 36 citations and is from a highest quality peer-reviewed journal.

  16. (kawano2024antitumoractivityof pages 1-2): SATOSHI KAWANO, MEGUMI IKEMORI KAWADA, SAYO FUKUSHIMA, YASUHITO ARAI, TATSUHIRO SHIBATA, and SAORI WATANABE MIYANO. Antitumor activity of tasurgratinib as an orally available fgfr1-3 inhibitor in cholangiocarcinoma models with fgfr2-fusion. AntiCancer Research, 44:2393-2406, May 2024. URL: https://doi.org/10.21873/anticanres.17046, doi:10.21873/anticanres.17046. This article has 7 citations and is from a peer-reviewed journal.

  17. (crolley2024…locally pages 2-3): V Crolley and J Bridgewater. … , locally advanced or metastatic intrahepatic cholangiocarcinoma with fibroblast growth factor receptor 2 (fgfr2) gene fusions or other rearrangements. Unknown journal, 2024.

  18. (facchinetti2024understandingandovercoming pages 2-3): Francesco Facchinetti, Yohann Loriot, Floriane Brayé, Damien Vasseur, Rastislav Bahleda, Ludovic Bigot, Rémy Barbé, Catline Nobre, David Combarel, Stefan Michiels, Antoine Italiano, Cristina Smolenschi, Lambros Tselikas, Jean-Yves Scoazec, Santiago Ponce-Aix, Benjamin Besse, Fabrice André, Ken A. Olaussen, Antoine Hollebecque, and Luc Friboulet. Understanding and overcoming resistance to selective fgfr inhibitors across fgfr2-driven malignancies. Clinical Cancer Research, 30:4943-4956, Sep 2024. URL: https://doi.org/10.1158/1078-0432.ccr-24-1834, doi:10.1158/1078-0432.ccr-24-1834. This article has 33 citations and is from a highest quality peer-reviewed journal.