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胰腺癌表观遗传学的进展:从机制到临床

Advances in pancreatic cancer epigenetics: From the mechanism to the clinic.

作者信息

Zhou Jia-Dan, Shen Hong-Zhang

机构信息

Department of Gastroenterology, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China.

Department of Gastroenterology, Hangzhou First People's Hospital, Hangzhou 310000, Zhejiang Province, China.

出版信息

World J Gastrointest Oncol. 2025 Jul 15;17(7):106238. doi: 10.4251/wjgo.v17.i7.106238.

Abstract

Pancreatic cancer (PC) is a highly malignant digestive system cancer that is difficult to diagnose early and is highly resistant to conventional treatments. Recent studies on epigenetics have provided new insights into the early diagnosis of PC and treatments including immunotherapy. Epigenetic changes can alter gene expression without altering the DNA sequence, involving mechanisms such as DNA methylation, histone modification, and the abnormal expression of noncoding RNAs. These mechanisms play crucial roles in the occurrence, development, and therapeutic response of tumors. This review summarizes progress in epigenetic research on PC and discusses the epigenetic characteristics, underlying mechanisms, early diagnosis, prognostic evaluation, treatment strategies, and future challenges for PC. Strategies targeting epigenetic changes may restore the expression of tumor suppressor genes and regulate the immune microenvironment and may be combined with immune checkpoint inhibitors as a new approach for the precise treatment of PC. However, there are challenges associated with the clinical application of epigenetic therapy, such as the development of resistance and adverse side effects, and challenges in target selection, so new epigenetic drugs and combination treatment strategies are needed. With the development of precision medicine, the integration of epigenetics and clinical medicine research has yielded broadly applicable findings. Interdisciplinary cooperation and advancements in clinical trials will further promote the application of epigenetics in PC research, providing more effective treatment options for patients. In the future, the combined application of epigenetic therapy and immunotherapy, the design of personalized treatment plans, and the development of technologies such as liquid biopsy will likely change the treatment landscape of PC.

摘要

胰腺癌(PC)是一种高度恶性的消化系统癌症,早期难以诊断,且对传统治疗具有高度抗性。近期关于表观遗传学的研究为胰腺癌的早期诊断及包括免疫疗法在内的治疗提供了新的见解。表观遗传变化可在不改变DNA序列的情况下改变基因表达,涉及DNA甲基化、组蛋白修饰和非编码RNA异常表达等机制。这些机制在肿瘤的发生、发展及治疗反应中发挥着关键作用。本综述总结了胰腺癌表观遗传学研究的进展,并讨论了胰腺癌的表观遗传特征、潜在机制、早期诊断、预后评估、治疗策略及未来挑战。针对表观遗传变化的策略可能恢复抑癌基因的表达并调节免疫微环境,还可与免疫检查点抑制剂联合使用,作为胰腺癌精准治疗的新方法。然而,表观遗传治疗的临床应用存在挑战,如耐药性的产生和不良副作用,以及靶点选择方面的挑战,因此需要新的表观遗传药物和联合治疗策略。随着精准医学的发展,表观遗传学与临床医学研究的整合已产生广泛适用的研究结果。跨学科合作及临床试验的进展将进一步推动表观遗传学在胰腺癌研究中的应用,为患者提供更有效的治疗选择。未来,表观遗传治疗与免疫治疗的联合应用、个性化治疗方案的设计以及液体活检等技术的发展可能会改变胰腺癌的治疗格局。

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