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Oncogenesis in cholangiocarcinoma
Rares Ilie Orzan1, Andrada Seicean1
13rd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, and Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania.
Advances in Clinical Chemistry
|January 22, 2026
Summary
Cholangiocarcinoma (CCA) is a complex biliary tract cancer driven by genetic mutations and signaling pathway dysregulation. Understanding these molecular drivers is key to developing targeted therapies for this challenging disease.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cholangiocarcinoma (CCA) is a heterogeneous biliary tract malignancy with increasing incidence and poor prognosis.
- Its development involves intricate interactions of environmental, infectious, and genetic factors.
- Understanding CCA oncogenesis is crucial for improving patient outcomes.
Purpose of the Study:
- To provide an in-depth analysis of current knowledge on CCA oncogenesis.
- To focus on subtypes, cellular origins, and the genetic/epigenetic landscape of CCA.
- To explore key molecular pathways and etiological factors involved in CCA.
Main Methods:
- Comprehensive literature review of CCA pathogenesis.
- Analysis of genetic alterations (mutations, tumor suppressor inactivation).
- Examination of dysregulated signaling pathways and etiological factors.
Main Results:
- Identified key oncogenic mutations (KRAS, BRAF, IDH1/2, PIK3CA) and tumor suppressor inactivation (TP53, CDKN2A, ARID1A, SMAD4, BAP1).
- Detailed the roles of RTK/PI3K/AKT/mTOR, MAPK/ERK, Wnt/β-catenin, TGF-β, Notch, and Hedgehog pathways.
- Highlighted contributions of inflammation, infections (liver fluke), viral hepatitis, and carcinogens.
Conclusions:
- CCA oncogenesis is driven by a complex interplay of genetic, epigenetic, and environmental factors.
- Dysregulation of major signaling pathways is central to CCA initiation and progression.
- A comprehensive understanding of CCA molecular mechanisms is vital for advancing precision medicine and targeted therapies.
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