Shahani Aanya, Slika Hasan, Elbeltagy Ahmad, Lee Alexandra, Peters Christopher, Dotson Toriyn, Raj Divyaansh, Tyler Betty
Hunterian Neurosurgical Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Cancer Drug Resist. 2025 Mar 13;8:12. doi: 10.20517/cdr.2024.157. eCollection 2025.
Glioblastoma (GBM) is an aggressive malignant brain tumor with almost inevitable recurrence despite multimodal management with surgical resection and radio-chemotherapy. While several genetic, proteomic, cellular, and anatomic factors interplay to drive recurrence and promote treatment resistance, the epigenetic component remains among the most versatile and heterogeneous of these factors. Herein, the epigenetic landscape of GBM refers to a myriad of modifications and processes that can alter gene expression without altering the genetic code of cancer cells. These processes encompass DNA methylation, histone modification, chromatin remodeling, and non-coding RNA molecules, all of which have been found to be implicated in augmenting the tumor's aggressive behavior and driving its resistance to therapeutics. This review aims to delve into the underlying interactions that mediate this role for each of these epigenetic components. Further, it discusses the two-way relationship between epigenetic modifications and tumor heterogeneity and plasticity, which are crucial to effectively treat GBM. Finally, we build on the previous characterization of epigenetic modifications and interactions to explore specific targets that have been investigated for the development of promising therapeutic agents.
胶质母细胞瘤（GBM）是一种侵袭性恶性脑肿瘤，尽管采用手术切除和放化疗等多模式治疗，但其复发几乎不可避免。虽然有多种遗传、蛋白质组学、细胞和解剖学因素相互作用导致复发并促进治疗抵抗，但表观遗传因素仍是这些因素中最具多样性和异质性的因素之一。在此，GBM的表观遗传格局是指无数可改变基因表达而不改变癌细胞遗传密码的修饰和过程。这些过程包括DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA分子，所有这些都被发现与增强肿瘤的侵袭性行为和驱动其对治疗的抵抗有关。本综述旨在深入探讨介导这些表观遗传成分各自发挥此作用的潜在相互作用。此外，还讨论了表观遗传修饰与肿瘤异质性和可塑性之间的双向关系，这对于有效治疗GBM至关重要。最后，我们基于之前对表观遗传修饰和相互作用的描述，探索已被研究用于开发有前景治疗药物的特定靶点。
