Cancer / Oncology/Cholangiocarcinoma
Hepatobiliary · type
Cholangiocarcinoma
Clinical / Scientific
Biliary adenocarcinomas include IDH1, FGFR2 fusion, KRAS and HER2 subsets, dense and inflammatory cholestatic niches. Targeted and checkpoint strategies are molecularly selected. Metabolic/stromal adjuncts remain investigational.
Core Biological Drivers
FGFR2 fusions / IDH1
Actionable subsets.
KRAS / TP53
More aggressive subsets.
Desmoplasia
Biliary CAF programmes.
Key Pathways
Scientific explanation
RAS GTPases and RAF kinases are frequent oncogenic nodes. KRAS, NRAS and BRAF mutations lock mitogenic signalling on in a ligand-independent way in many tumours.
Scientific explanation
HER2/ERBB2 amplification or overexpression produces ligand-independent ERBB signalling, classically in a subset of breast and gastroesophageal cancers and rarely in colorectal cancer.
Scientific explanation
TGF-β is cytostatic in intact epithelium but later supports , immune suppression and stromal . Context switches its role during progression.
Scientific explanation
Canonical Wnt signalling stabilizes β-catenin, driving TCF/LEF . APC loss is a classic colorectal initiating event; the pathway also contributes to stemness in several tissues.
Scientific explanation
family ligands drive endothelial sprouting and vascular permeability, a canonical tumour axis.
Scientific explanation
PD-1 on T cells engaging PD-L1/PD-L2 restrains cytotoxic function. Tumour or myeloid PD-L1 is a canonical adaptive immune-evasion axis.
Scientific explanation
Aerobic (Warburg metabolism) supports ATP, biomass and redox buffering even when oxygen is available. Hexokinase, PKM2 and lactate export are frequent nodes.
Scientific explanation
Epithelial–mesenchymal plasticity, driven by TWIST/SNAIL/ZEB and TGF-β/Wnt/Notch inputs, reduces adhesion and increases motility and stem-like features.
Pathway Convergence
Target → pathway → downstream effect → biological consequence. Shared intersections are mechanistic maps, not protocols.
Growth-factor signalling
Ligand or mutation-driven RTK input feeds PI3K/AKT and mTORC1, supporting anabolic growth. This is a map of signalling, not a treatment protocol.
Stroma and TGF-β
Desmoplastic stroma and TGF-β can compress vessels and exclude T cells. Stromal adjuncts aim at the neighbourhood, not at a single oncogene.
Hypoxia to vessels
Low oxygen stabilizes HIF-1α, inducing VEGF and endothelial sprouting. Anti-angiogenic pharmacology intersects this axis but does not erase the tumour ecosystem.
Metabolic Vulnerabilities
Aerobic supports ATP, biomass and acidification even when oxygen is available. Extent varies by tumour and remains a vulnerability hypothesis rather than a uniform target.
IDH-mutant tumours produce 2-hydroxyglutarate and rewire epigenetics.
Tumor Microenvironment
Cancer-associated fibroblasts, TGF-β and extracellular-matrix stiffness can compress vessels and exclude T cells, especially in desmoplastic tumours.
Disordered vasculature creates , HIF-1α stabilization, induction and immune-suppressive adenosine/lactate milieus.
Metastasis Module
, protease-mediated invasion, , circulating tumour-cell survival and organ-specific colonization form the metastatic cascade. Pre-metastatic niches and vascular permeability influence tropism.
Resistance Biology
Resistance can arise from drug efflux, secondary mutations, bypass RTK signalling, apoptotic threshold elevation, -mediated survival, metabolic adaptation and lineage plasticity.
Cancer Stemness
Wnt, Notch, Hedgehog, ALDH and CD44-associated programmes can mark stem-like fractions with quiescence and therapy tolerance. These markers are not interchangeable across tumour types.
Mechanism-Based Adjunctive Strategies
Compounds appear only where a mechanistic overlap exists for this cancer. Evidence tiers are not equivalent. Nothing here is a treatment recommendation.
Losartan
Target / Mechanism
AT1- . In desmoplastic models, angiotensin blockade can reduce TGF-β-linked stromal compression and improve perfusion; this is adjunctive stromal biology, not cytotoxic oncology.
Cancer relevance
AT1 blockade can reduce TGF-β-linked desmoplasia and improve perfusion in models, notably pancreatic. Stromal decompression is not cytotoxicity.
Stroma / perfusion adjunctive research. Convergence: TGF-β, Angiogenesis.
Target / Mechanism
Modest complex I inhibition raises AMP:ATP, activating and restraining hepatic and -linked anabolism. Direct antineoplastic efficacy is not established from that pharmacology alone.
Cancer relevance
activation and restraint provide a metabolic rationale in - and -linked tumours. Human data are mixed and do not establish metformin as cancer therapy.
Metabolic adjunctive research context. Convergence: AMPK, mTOR, Glycolysis.
Curcumin
Target / Mechanism
Polyphenol with promiscuous in-vitro NF-κB, and ROS effects. Bioavailability is poor; dish activity does not establish clinical anticancer efficacy.
Cancer relevance
In-vitro NF-κB/ effects are frequent. Poor bioavailability and absence of robust clinical anticancer efficacy keep this pathway-level.
Inflammatory-signalling dish models. Convergence: NF-κB, JAK/STAT.
Target / Mechanism
Azole antifungal; off-target reports include Hedgehog-pathway antagonism and anti-angiogenic endothelial effects in experimental and early clinical settings. Not a licensed antineoplastic.
Cancer relevance
Hedgehog antagonism and anti-angiogenic endothelial reports exist, including early clinical probes. Not a licensed antineoplastic.
Hedgehog / angiogenesis research. Convergence: Hedgehog, Angiogenesis.
Research Context
- Hallmarks. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674. https://doi.org/10.1016/j.cell.2011.02.013
- Resistance. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13(10):714-726. https://doi.org/10.1038/nrc3599
This oncology atlas is educational. Pathway maps, adjunctive strategies, and compound listings describe mechanistic relevance. They do not establish clinical efficacy, do not recommend treatment, and are not a substitute for oncology care. Evidence tiers are not equivalent.