Breaking epigenetic shackles: targeting ARID1A methylation and the PI3K/AKT/mTOR-PD-L1 axis to overcome immune escape in gastric cancer

ARID1A promoter hypermethylation drives an epigenetic-immune checkpoint cascade in GC. Combined with its association with immune signatures and PD-L1 upregulation, ARID1A hypermethylation emerges as a candidate biomarker for predicting immune checkpoint blockade (ICB) responsiveness and patient stratification in GC. Future studies should evaluate 5-aza-CdR-ICB-AKT inhibitor regimens in advanced models to guide clinical translation.