Molecular Testing for Intrahepatic Cholangiocarcinoma: What, When, How?
Molecular testing has become an essential component of modern intrahepatic cholangiocarcinoma (iCCA) management, enabling early identification of actionable genomic alterations and facilitating precision oncology.
Intrahepatic cholangiocarcinoma (iCCA) represents a biologically heterogeneous subgroup of biliary tract cancer (BTC) with a 5‑year survival below 20%. Delayed diagnosis, intrinsic aggressiveness, and extensive inter‑tumoral and intra‑tumoral heterogeneity at the clinical, histopathological, and genomic level all contribute to this dismal outcome. Increasingly, treatment decisions in advanced iCCA depend on the identification of actionable molecular alterations, including FGFR2 fusions or rearrangements, IDH1 mutations, HER2 amplifications, NTRK fusions, and microsatellite instability (MSI‑high) and/or mismatch repair deficiency (dMMR). A narrative review of the current literature was conducted, focusing on (i) what molecular alterations are clinically relevant today, (ii) when molecular profiling should be performed, and (iii) how testing should be technically implemented in routine clinical practice. Results iCCA, particularly the small‑duct subtype, harbors a high prevalence of therapeutically actionable molecular alterations, in contrast to extrahepatic cholangiocarcinoma and gallbladder carcinoma. Early and comprehensive molecular profiling enables access to approved targeted therapies, molecularly stratified second‑line treatments, and clinical trials. Combined DNA‑ and RNA‑based next‑generation sequencing, complemented by immunohistochemistry and in situ hybridization, provides the most reliable diagnostic framework.
The survival advantage for iCCA patients is contingent on timely and comprehensive molecular profiling to match patients with available precision therapies or clinical trials, thereby improving outcomes in this aggressive malignancy.
Evidence level: Állatkísérletes. Állatmodellben vizsgálták.
Related signals
- The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma
- Scientists build cell line atlas of deadly cancers of the bile ducts and gallbladder
- Cholangiocarcinoma Workup: Laboratory Studies, Imaging Studies, Procedures
- New EASL Clinical Practice Guidelines on extrahepatic cholangiocarcinoma
- An open‑label study of pemigatinib in cholangiocarcinoma: final results from FIGHT‑202