Drug resistance remains one of the greatest obstacles to successful treatment of gastric cancer , limiting the long-term effectiveness of the widely used chemotherapy drug cisplatin . A new review highlights autophagy , the natural process by which cells recycle damaged proteins and organelles, as a promising therapeutic target that could improve treatment responses and help overcome resistance to chemotherapy.
Gastric cancer is among the leading causes of cancer-related deaths worldwide, with many patients developing resistance to cisplatin during treatment. The review explains that this resistance arises through multiple biological mechanisms, including enhanced DNA repair, reduced cell death, changes in the tumor microenvironment, and alterations in cellular signaling pathways. Increasing evidence indicates that autophagy plays a central role in many of these processes, making it an attractive target for new treatment strategies.
The article describes the complex nature of autophagy , which can either protect cancer cells from the effects of chemotherapy or promote their destruction, depending on the biological context. This dual role means that carefully controlling autophagy could make gastric cancer cells more vulnerable to cisplatin while limiting the mechanisms that allow tumors to survive treatment.
The review brings together evidence on a wide range of existing medicines and experimental compounds that influence autophagy . Several established drugs, including diclofenac , metformin , chloroquine , omeprazole , ubenimex , and bortezomib , are discussed for their potential to enhance the effectiveness of cisplatin by either stimulating cancer-killing autophagy or blocking the protective form of the process that contributes to drug resistance. Natural compounds such as glycyrrhizin , baicalein , red ginseng polysaccharide , and α-mangosteen are also identified as promising candidates.
In addition to drug-based approaches, the review identifies numerous molecular targets involved in regulating autophagy, including signaling pathways, transcription factors, microRNAs, and proteins associated with tumor survival. These targets may support the development of more precise therapies designed to restore chemotherapy sensitivity while reducing the likelihood of resistance.
The review also emphasizes the potential for combining autophagy modulation with other treatment approaches, including immunotherapy , radiotherapy , and precision medicine strategies. Tailoring treatment according to the biological characteristics of individual tumors may further improve outcomes for patients whose cancers no longer respond to conventional chemotherapy.
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Reference
Luling Wei, Yingfei Zhou, Jiashuo Li, Hongzhao Qi, Shasha Wang, Autophagy as a therapeutic target for cisplatin-resistant gastric cancer, Genes & Diseases, Volume 13, Issue 5, 2026, 101992, ISSN 2352-3042, https://doi.org/10.1016/j.gendis.2025.101992
Funding
Natural Science Foundation of Shandong Province, China ZR2024ME020)
Wu Jieping Medical Foundation 320.6750.2024-18.66
Affiliated Hospital of Qingdao University Clinical Medicine+X (Shandong, China) QDFY+X2023104)
Genes & Diseases