Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States.
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Curr Probl Cancer. 2024 Oct;52:101131. doi: 10.1016/j.currproblcancer.2024.101131. Epub 2024 Aug 21.
Neuroendocrine tumors (NETs) are a rare, heterogenous group of neoplasms arising from cells of the neuroendocrine system. Amongst solid tumor malignancies, NETs are notable for overall genetic stability and recent data supports the notion that epigenetic changes may drive NET pathogenesis. In this review, major epigenetic mechanisms of NET pathogenesis are reviewed, including changes in DNA methylation, histone modification, chromatin remodeling, and microRNA. Prognostic implications of the above are discussed, as well as the expanding diagnostic utility of epigenetic markers in NETs. Lastly, preclinical and clinical evaluations of epigenetically targeted therapies in NETs and are reviewed, with a focus on future directions in therapeutic advancement.
神经内分泌肿瘤（NETs）是一组起源于神经内分泌系统细胞的罕见、异质性肿瘤。在实体肿瘤恶性肿瘤中，NET 以整体遗传稳定性为特征，最近的数据支持表观遗传变化可能驱动 NET 发病机制的观点。在这篇综述中，回顾了 NET 发病机制的主要表观遗传机制，包括 DNA 甲基化、组蛋白修饰、染色质重塑和 microRNA 的变化。讨论了上述因素的预后意义，以及表观遗传标记在 NET 中的诊断应用不断扩大。最后，综述了 NET 中针对表观遗传靶点的治疗的临床前和临床评估，重点关注治疗进展的未来方向。
