Intrahepatic Cholangiocarcinoma: Emerging Insights from Pathobiology to Clinical Translation – Innovative Strategies, Challenges, and Opportunities

Intrahepatic cholangiocarcinoma (ICC) presents as a lethal form of liver cancer, characterized by increasing global incidence and inherent complexities including delayed diagnosis, complex molecular heterogeneity, and limited therapeutic efficacy. Despite advancements in surgical and systemic treatments, the 5-year survival rate remains below 20%, highlighting the critical need for a deeper understanding of its pathogenesis and novel clinical strategies. Recent research breakthroughs highlighting driver mutations (e.g., FGFR2, IDH1/2) and dysregulated pathways in molecular profiling show great promise, yet challenges persist in translating these discoveries into durable clinical benefits. The immunosuppressive tumor microenvironment (TME), chemoresistance mechanisms, and the lack of reliable biomarkers further complicate therapeutic progress. Beyond treatment, gaps in early detection methods, prognostic models, and multidisciplinary care integration underscore the necessity for holistic approaches. Emerging fields such as liquid biopsy, epigenetics, and artificial intelligence-driven diagnostics offer transformative potential, however, their clinical utility in ICC remains underexplored.

This Research Topic seeks to advance the understanding and management of ICC by integrating multidisciplinary insights from molecular biology, immunology, clinical oncology, and translational research. We aim to address unmet needs across the disease continuum—from early detection and risk stratification to novel therapeutic strategies and survivorship care. By emphasizing both mechanistic discoveries and clinical applications, this collection will highlight innovative approaches to overcome resistance, optimize patient stratification, and improve outcomes. Contributions that explore the interplay between tumor biology, host immunity, and therapeutic interventions are strongly encouraged.

We welcome original research, reviews, clinical trials, meta-analyses, and perspective articles addressing, but not limited to:
-Molecular Pathogenesis: Genetic/epigenetic drivers, metabolic reprogramming, and ICC heterogeneity.
-Diagnostic Innovations: Liquid biopsies, imaging advancements, and AI-based diagnostic tools.
-Therapeutic Frontiers: Targeted therapies (e.g., FGFR/IDH inhibitors), immunotherapies, nanotechnology, and combination strategies.
-TME and Resistance Mechanisms: Stromal interactions, immune evasion, and strategies to reprogram the TME.
-Translational Biomarkers: Predictive/prognostic biomarkers for treatment response and recurrence monitoring.
-Multimodal Integration: Synergy between systemic therapies, surgery, radiotherapy, and interventional radiology.
-Preclinical Models: Patient-derived organoids, murine models, and 3D bioprinting for drug discovery.
-Clinical Challenges: Management of advanced/metastatic ICC, survivorship, and quality-of-life studies.

Submissions should emphasize innovation, translational relevance, or clinical impact. Interdisciplinary studies bridging basic science and real-world applications are prioritized. All manuscripts will undergo rigorous peer review to ensure scientific excellence and originality.

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Intrahepatic Cholangiocarcinoma, Translational Oncology, Precision Oncology, Tumor Microenvironment, Multimodal Therapies

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.