The m6A-circRNA axis: a therapeutic prospect for gastric cancer

Gastric cancer (GC) remains a major global health burden, and resistance to conventional therapies continues to limit durable clinical benefit. Increasing evidence identifies the N6-methyladenosine (m6A)–circular RNAs (circRNAs) axis as a critical regulatory network driving GC progression and therapeutic resistance. The functional interplay between m6A RNA modification and circRNAs contributes to key oncogenic processes, including chemoresistance, immune evasion, metabolic reprogramming, and resistance to cell death. In particular, m6A-modified circRNAs promote tumor progression by enhancing transcript stability, facilitating oncogenic signaling, modulating immune checkpoint pathways, and supporting metabolic adaptation under therapeutic stress. In this review, we synthesize current advances in understanding the mechanistic and translational significance of the m6A–circRNA axis in GC. We examine how this regulatory interface orchestrates adaptive resistance and evaluate emerging therapeutic strategies aimed at targeting its components. Modulating the m6A–circRNA axis—either as a standalone approach or in combination with existing treatments—represents a promising strategy to overcome multidrug resistance and improve clinical outcomes in GC.