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Molecular Testing for Intrahepatic Cholangiocarcinoma: What, When, How?

Maryam Barsch1, Elaine-Pashupati Dopfer2,3, Anne Maria Schultheis2,3

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|January 14, 2026
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Summary
This summary is machine-generated.

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).

Keywords:
Biliary tract cancerIntrahepatic cholangiocarcinomaMolecular profilingNext-generation sequencingPrecision oncologyTargeted therapy

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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.