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Autophagy as a therapeutic target for cisplatin-resistant gastric cancer
Genes & Diseases 2026, 13(5)
Published: 19 December 2025
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Cisplatin is widely employed in the treatment of gastric cancer (GC). However, the resistance mechanisms exhibited by GC cells often result in suboptimal clinical outcomes associated with cisplatin therapy. Autophagy, a self-degradative cellular process, plays a complex dual role in regulating tumor cell death and survival. In recent years, significant attention has been directed toward the relationship between autophagy and cisplatin resistance in GC, fostering the development of various autophagy-related drugs and potential targets aimed at enhancing the sensitivity of GC cells to cisplatin. Nevertheless, a comprehensive analysis of the correlations among relevant studies is still lacking. This review synthesizes recent research examining the impact of autophagy on cisplatin resistance in GC cells, with particular emphasis on existing drugs and potential therapeutic drugs/targets. It briefly explores the fundamental processes of autophagy and clarifies the relationship between autophagy mechanisms and GC. Furthermore, it summarizes the available drugs and potential candidates that can either enhance or inhibit autophagy, thereby improving GC cell sensitivity to cisplatin, alongside their underlying mechanisms. Additionally, it consolidates pertinent research findings to present a more thorough understanding of the intricate relationships between autophagy and cisplatin resistance in GC cells. We hope this review will encourage researchers to investigate novel mechanisms of cisplatin resistance in GC cells, discover new targeted therapies, and propose innovative strategies to tackle this challenge.

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