Xia Zhelin, Kong Fanhua, Wang Kunpeng, Zhang Xin
Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.
Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, China.
Front Pharmacol. 2022 Jun 9;13:908079. doi: 10.3389/fphar.2022.908079. eCollection 2022.
Digestive system tumours, including stomach, colon, esophagus, liver and pancreatic tumours, are serious diseases affecting human health. Although surgical treatment and postoperative chemoradiotherapy effectively improve patient survival, current diagnostic and therapeutic strategies for digestive system tumours lack sensitivity and specificity. Moreover, the tumour's tolerance to drug therapy is enhanced owing to tumour cell heterogeneity. Thus, primary or acquired treatment resistance is currently the main hindrance to chemotherapy efficiency. N6-methyladenosine (m6A) has various biological functions in RNA modification. m6A modification, a key regulator of transcription expression, regulates RNA metabolism and biological processes through the interaction of m6A methyltransferase ("writers") and demethylase ("erasers") with the binding protein decoding m6A methylation ("readers"). Additionally, m6A modification regulates the occurrence and development of tumours and is a potential driving factor of tumour drug resistance. This review systematically summarises the regulatory mechanisms of m6A modification in the drug therapy of digestive system malignancies. Furthermore, it clarifies the related mechanisms and therapeutic prospects of m6A modification in the resistence of digestive system malignancies to drug therapy.
消化系统肿瘤，包括胃癌、结肠癌、食管癌、肝癌和胰腺癌，是影响人类健康的严重疾病。尽管手术治疗和术后放化疗有效地提高了患者的生存率，但目前消化系统肿瘤的诊断和治疗策略缺乏敏感性和特异性。此外，由于肿瘤细胞的异质性，肿瘤对药物治疗的耐受性增强。因此，原发性或获得性治疗耐药性是目前化疗疗效的主要障碍。N6-甲基腺苷（m6A）在RNA修饰中具有多种生物学功能。m6A修饰作为转录表达的关键调节因子，通过m6A甲基转移酶（“书写者”）和去甲基化酶（“擦除者”）与解码m6A甲基化的结合蛋白（“阅读者”）的相互作用来调节RNA代谢和生物学过程。此外，m6A修饰调节肿瘤的发生发展，是肿瘤耐药性的潜在驱动因素。本文综述系统总结了m6A修饰在消化系统恶性肿瘤药物治疗中的调控机制。此外，还阐明了m6A修饰在消化系统恶性肿瘤对药物治疗耐药中的相关机制和治疗前景。
