RNA m6A modification is a driver and therapeutic target in gastric cancer.

N6-methyladenosine (m6A), the most abundant modification in eukaryotic RNAs, plays a critical role in regulating RNA stability, expression, and translation. Key m6A regulators are up- or down-regulated in human gastric cancer tissues, by Helicobacter pylori and transcription factors, and the aberrant expression is associated with poor patient prognosis. Dynamic m6A modification, orchestrated by methyltransferases, demethylases, and m6A-binding proteins, profoundly impacts gastric cancer tumorigenesis, metastasis, cancer cell stemness, immune evasion, and resistance to chemotherapy, radiotherapy, and immunotherapy. While aberrant m6A modifications and the expression levels of its regulatory factors in blood samples are novel biomarkers in gastric cancer patients, therapies targeting m6A regulators have emerged as promising approaches for treating the disease. In summary, m6A RNA methylation represents a pivotal epitranscriptomic mechanism with significant implications for gastric cancer biology and precision oncology.