Cancer / Oncology/MSI-high colorectal cancer
Gastrointestinal · subtype
MSI-high colorectal cancer
Subtype of Colorectal cancer
Clinical / Scientific
Mismatch-repair deficiency creates frameshift neoantigens and high PD-1/PD-L1 axis relevance. Immune-checkpoint blockade is established in this molecular subset. Wnt/KRAS events may still occur but immune visibility dominates therapeutic logic.
Core Biological Drivers
MMR loss
MLH1 methylation or Lynch syndrome mutations.
Neoantigen load
Frameshift peptides.
PD-1 axis
Adaptive immune resistance.
Key Pathways
Scientific explanation
Homologous-recombination defects (BRCA1/2 and related) create dependence on PARP-mediated repair. Mismatch-repair deficiency creates hypermutation and immune visibility.
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
CTLA-4 competes with CD28 for B7 ligands, restraining priming of T cells mainly in lymphoid tissues and Tregs.
Scientific explanation
Tumours recruit Tregs, MDSCs and M2-like macrophages, and secrete TGF-β, IL-10, adenosine and IDO-related metabolites to blunt effector immunity.
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
-2–PGE2 signalling can promote , immune suppression and epithelial proliferation, notably in colorectal neoplasia.
Pathway Convergence
Target → pathway → downstream effect → biological consequence. Shared intersections are mechanistic maps, not protocols.
Inflammatory survival
Chronic cytokine tone activates NF-κB and STAT3 transcriptional programmes that favour survival, invasion and sometimes immune evasion.
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
Tumour-associated macrophages and myeloid-derived suppressor cells secrete cytokines that support invasion and blunt cytotoxic T cells.
High cytotoxic T-cell infiltration is typical but not universal.
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
Immuno-editing, JAK/MHC defects and alternative checkpoints can cause immunotherapy resistance.
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.
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.
Beta-glucans / medicinal-mushroom polysaccharides
Target / Mechanism
β-glucans can engage Dectin-1 and complement pathways, modulating innate immunity in models and some adjunctive clinical settings. They are not tumour-selective cytotoxics.
Cancer relevance
Innate-immune engagement via Dectin-1-related biology. Adjunctive immunomodulation is not tumour-selective cytotoxicity.
Innate-immune adjunctive research. Convergence: Immune suppression.
Omega-3 fatty acids
Target / Mechanism
EPA/DHA alter eicosanoid balance and membrane signalling. Cachexia and hypotheses exist; they are not cytotoxic oncology drugs.
Cancer relevance
Eicosanoid rebalancing and cachexia/ research. Not cytotoxic oncology.
Inflammation / cachexia supportive research. Convergence: COX / inflammatory signalling, Immune suppression.
Research Context
- CRC TCGA. The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330-337. https://doi.org/10.1038/nature11252
- 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
- Immune landscape. Thorsson V, et al. The Immune Landscape of Cancer. Immunity. 2018;48(4):812-830.e14. https://doi.org/10.1016/j.immuni.2018.03.023
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.