Cancer / Oncology/Mesothelioma
Thoracic · type
Mesothelioma
Clinical / Scientific
Mesothelioma arises from mesothelial surfaces, often with asbestos-related , BAP1/CDKN2A/NF2 alterations, Hippo-pathway dysregulation, and dense . Immune-checkpoint combinations have entered selected practice; metabolic and stromal adjuncts remain largely investigational.
Core Biological Drivers
BAP1 / CDKN2A / NF2
Tumour-suppressor losses including Hippo-pathway NF2.
Chronic inflammation
Asbestos-related milieu.
Angiogenesis
-high biology historically.
Key Pathways
Scientific explanation
family ligands drive endothelial sprouting and vascular permeability, a canonical tumour axis.
Scientific explanation
-inducible factors stabilize when oxygen is low, shifting toward , and survival.
Scientific explanation
phosphorylates PIP2 to PIP3, recruiting . supports growth, survival, glucose uptake and mTORC1 input. Pathway activation is common via PIK3CA mutation, PTEN loss or -tyrosine- signalling.
Scientific explanation
NF-κB factors link inflammatory cytokines and innate sensors to survival, production and sometimes therapy resistance.
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
TGF-β is cytostatic in intact epithelium but later supports , immune suppression and stromal . Context switches its role during progression.
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
Hippo signalling restrains YAP/TAZ transcriptional co-activators. NF2 loss, common in mesothelioma, derepresses YAP-driven growth programmes.
Pathway Convergence
Target → pathway → downstream effect → biological consequence. Shared intersections are mechanistic maps, not protocols.
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.
Inflammatory survival
Chronic cytokine tone activates NF-κB and STAT3 transcriptional programmes that favour survival, invasion and sometimes immune evasion.
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.
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.
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.
Tumour-associated macrophages and myeloid-derived suppressor cells secrete cytokines that support invasion and blunt cytotoxic T cells.
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.
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.
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.
Celecoxib
Target / Mechanism
Selective -2 reducing PGE2. Relevant to -associated epithelial neoplasia; cardiovascular risk and lack of broad anticancer approval constrain interpretation.
Cancer relevance
-2/PGE2 biology is relevant in some epithelial neoplasias. Cardiovascular risk and lack of broad anticancer approval apply. Do not equate polyp or biomarker studies with tumour cure.
Inflammation-associated epithelial neoplasia research. Convergence: COX / inflammatory signalling, Angiogenesis.
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.
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.
Research Context
- Angiogenesis. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature. 2005;438(7070):967-974. https://doi.org/10.1038/nature04478
- 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
- Checkpoints. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264. https://doi.org/10.1038/nrc3239
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.