Xu Ziyi, Sun Bo, Wang Weizheng, Fan Yitao, Su Jingxiang, Sun Jiachun, Gu Xinyu
Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China.
Front Pharmacol. 2025 Apr 28;16:1565738. doi: 10.3389/fphar.2025.1565738. eCollection 2025.
Gastrointestinal (GI) tumors represent a significant global health burden and are among the leading causes of cancer-related mortality worldwide. their drug resistance is one of the major challenges in cancer therapy. In recent years, epigenetic modifications, especially N6-methyladenosine (m6A) RNA modifications, have become a hot research topic. m6A modification plays an important role in gene expression and cancer progression by regulating RNA splicing, translation, stability, and degradation, which are regulated by "writers," "erasers" and "readers." In GI tumors, resistance to chemotherapy, targeted therapy, and immunotherapy is closely associated with m6A RNA modification. Therefore, the molecular mechanism of m6A modification and its targeted drug development provide new therapeutic strategies for overcoming drug resistance and therapeutic efficacy in GI tumors. In this review, the biological functions of m6A were explored, the specific resistance mechanisms of m6A in different types of GI tumors were explored, new ideas and targets for future treatment resistance were identified, and the limitations of this field were highlighted.
胃肠道（GI）肿瘤是一项重大的全球健康负担，也是全球癌症相关死亡的主要原因之一。其耐药性是癌症治疗中的主要挑战之一。近年来，表观遗传修饰，尤其是N6-甲基腺苷（m6A）RNA修饰，已成为一个热门研究课题。m6A修饰通过调节RNA剪接、翻译、稳定性和降解在基因表达和癌症进展中发挥重要作用，而这些过程由“书写器”“擦除器”和“读取器”调控。在胃肠道肿瘤中，对化疗、靶向治疗和免疫治疗的耐药性与m6A RNA修饰密切相关。因此，m6A修饰的分子机制及其靶向药物开发为克服胃肠道肿瘤的耐药性和提高治疗效果提供了新的治疗策略。在本综述中，探讨了m6A的生物学功能，探究了m6A在不同类型胃肠道肿瘤中的具体耐药机制，确定了未来治疗耐药性的新思路和靶点，并强调了该领域的局限性。
