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Molecular Testing for Intrahepatic Cholangiocarcinoma: What, When, How?
Maryam Barsch1, Elaine-Pashupati Dopfer2,3, Anne Maria Schultheis2,3
1Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, University Hospital Freiburg, Freiburg, Germany. maryam.barsch@uniklinik-freiburg.de.
Journal of Gastrointestinal Cancer
|January 14, 2026
Summary
Molecular profiling is crucial for intrahepatic cholangiocarcinoma (iCCA) patients. Early and comprehensive testing identifies actionable targets, improving treatment strategies and outcomes in biliary tract cancer (BTC).
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous biliary tract cancer (BTC) with poor survival rates.
- Delayed diagnosis and tumor heterogeneity complicate treatment for advanced iCCA.
- Identifying molecular alterations like FGFR2 fusions and IDH1 mutations is key for targeted therapies.
Purpose of the Study:
- To review clinically relevant molecular alterations in iCCA.
- To determine optimal timing for molecular profiling.
- To outline technical implementation of molecular testing in clinical practice.
Main Methods:
- A narrative literature review was conducted.
- Focus on actionable molecular alterations, timing, and technical implementation.
- Analysis of DNA- and RNA-based next-generation sequencing, IHC, and ISH.
Main Results:
- The small-duct subtype of iCCA shows a high prevalence of actionable molecular alterations.
- Early and comprehensive molecular profiling facilitates access to targeted therapies and clinical trials.
- Combined DNA/RNA sequencing with IHC/ISH offers a reliable diagnostic framework.
Conclusions:
- Molecular testing is integral to modern iCCA management.
- Broad, early, and integrated molecular profiling is essential for precision oncology in BTC.
- Interdisciplinary tumor board interpretation of results is critical.
