Molecular Mechanisms in Gastric Cancer Pathology

The development and progression of gastric cancer are driven by a complex interplay of genetic alterations, epigenetic modifications and aberrant signalling pathways. At the genomic level, chromosomal instability and microsatellite alterations give rise to oncogene activation and tumour suppressor loss. Key signalling cascades, including Wnt/β-catenin, Notch and PI3K/AKT, become dysregulated and foster uncontrolled proliferation, resistance to apoptosis and invasive behaviour. The process of epithelial-mesenchymal transition facilitates dissemination, while alterations in cell-cycle regulators such as cyclins and cyclin-dependent kinase inhibitors further disrupt growth control. Tumour microenvironmental factors, including hypoxia and inflammatory mediators, modulate angiogenesis and immune evasion. Epigenetic changes—such as DNA methylation of promoter regions and histone modifications—silence critical genes governing cell adhesion and DNA repair. Collectively, these molecular aberrations define distinct gastric cancer subtypes with varied prognoses and therapeutic vulnerabilities. Advances in genomic profiling and molecular phenotyping have paved the way for stratified treatment approaches, encompassing targeted inhibitors, immunotherapies and precision surgical strategies. Understanding these interlinked molecular mechanisms is crucial for improving early detection, prognostic assessment and the development of novel interventions to reduce the global burden of gastric cancer.

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Molecular Mechanisms in Gastric Cancer Pathology publication trend

The graph below shows the total number of articles in molecular mechanisms in gastric cancer pathology across all publications each year (not limited to Nature Index journals).

Technical terms

Copy number variation: A genomic alteration in which sections of DNA are duplicated or deleted, affecting gene dosage and potentially driving oncogenesis.

Epithelial-mesenchymal transition: A cellular programme by which epithelial cells acquire mesenchymal traits, enhancing motility, invasiveness and resistance to apoptosis.

Notch signalling pathway: A conserved cell-to-cell communication mechanism that regulates differentiation, proliferation and apoptosis through receptor–ligand interactions and target gene activation.

Mucin phenotype: The pattern of mucin glycoprotein expression (e.g. MUC2, MUC5AC, MUC6) in tumour cells, used to classify gastric cancers by their biological behaviour and differentiation status.

References

1. SPON2 Is Upregulated through Notch Signaling Pathway and Promotes Tumor Progression in Gastric Cancer. Cancers (2020).
2. High-Throughput Sequencing and Copy Number Variation Detection Using Formalin Fixed Embedded Tissue in Metastatic Gastric Cancer. PLOS ONE (2014).
3. Gastric mucin phenotype indicates aggressive biological behaviour in early differentiated gastric adenocarcinomas following endoscopic treatment. Diagnostic Pathology (2021).