摘要
近几十年来,全球胃癌发病率一直在下降。尽管诊断程序有所改善,但由于缺乏与肿瘤发展的早期阶段相关的特定症状,大多数病例仍在晚期检测到。因此,由于高死亡率,胃癌在全世界造成重大的健康负担。高通量技术的不断进步揭示了与致癌相关的遗传和表观遗传变化的复杂网络。此外,已经认识到几种危险因素,包括环境因素和遗传因素,这些因素促进了影响癌基因,肿瘤抑制基因,DNA修复基因和其他基因表达的各种改变的累积,这些改变涉及正常的胃细胞功能。患有这种疾病的患者中发现的过多的异常分子事件和来自个体的肿瘤的基因内异质性延迟了靶向生物疗法的发展。胃癌特别是与幽门螺杆菌或EBV感染相关的特征性CpG岛甲基化表型(CIMP表型)的频繁发生可能导致表观遗传调节剂被引入用于治疗早期和晚期腺癌的标准治疗方案中。这篇综述强调了胃癌发生过程中异常的DNA甲基化事件,并阐述了与治疗性表观遗传调控在疾病管理中的应用有关的不同方面。
关键词: 胃癌,DNA甲基化,miRNA,CpG岛,表观遗传修饰,幽门螺杆菌,治疗
Current Cancer Drug Targets
Title:Outlook on Epigenetic Therapeutic Approaches for Treatment of Gastric Cancer
Volume: 18 Issue: 1
关键词: 胃癌,DNA甲基化,miRNA,CpG岛,表观遗传修饰,幽门螺杆菌,治疗
摘要: The incidence of gastric cancer has been declining globally in the last decades. Despite the improvements in the diagnostic procedures, most cases are still detected at advanced stages due to lack of specific symptoms associated with early phases of tumour development. Consequently, gastric cancer poses a major health burden worldwide due to high mortality rates. Continuing advances in high-throughput technologies are revealing an intricate network of genetic and epigenetic changes associated with carcinogenesis. In addition, several risk factors, both environmental and genetic, have been recognized, which promote accumulation of diverse alterations affecting the expression of oncogenes, tumour suppressor genes, DNA repair genes, and other genes, implicated in normal gastric cell functions. A plethora of aberrant molecular events found in patients with this disease and intragenic heterogeneity of tumours from individuals are delaying the development of targeted biological therapies. Frequent occurrence of characteristic CpG island methylator phenotypes (CIMP phenotypes) in gastric cancers, particularly in association with Helicobacter pylori or EBV infection, could lead to introduction of epigenetic modulators into standard treatment regimens used against early and advanced forms of adenocarcinomas. This review highlights aberrant DNA methylation events in the development of gastric tumours and addresses the different aspects associated with the application of therapeutic epigenetic modulation in the management of the disease.
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Cite this article as:
Outlook on Epigenetic Therapeutic Approaches for Treatment of Gastric Cancer, Current Cancer Drug Targets 2018; 18 (1) . https://dx.doi.org/10.2174/1568009617666170203163745
DOI https://dx.doi.org/10.2174/1568009617666170203163745 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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