表观遗传修饰对胶质母细胞瘤适应性耐药进化的影响。
The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma.
机构信息
Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
出版信息
Int J Mol Sci. 2021 Aug 3;22(15):8324. doi: 10.3390/ijms22158324.
Glioblastoma (GBM) is a highly lethal cancer that is universally refractory to the standard multimodal therapies of surgical resection, radiation, and chemotherapy treatment. Temozolomide (TMZ) is currently the best chemotherapy agent for GBM, but the durability of response is epigenetically dependent and often short-lived secondary to tumor resistance. Therapies that can provide synergy to chemoradiation are desperately needed in GBM. There is accumulating evidence that adaptive resistance evolution in GBM is facilitated through treatment-induced epigenetic modifications. Epigenetic alterations of DNA methylation, histone modifications, and chromatin remodeling have all been implicated as mechanisms that enhance accessibility for transcriptional activation of genes that play critical roles in GBM resistance and lethality. Hence, understanding and targeting epigenetic modifications associated with GBM resistance is of utmost priority. In this review, we summarize the latest updates on the impact of epigenetic modifications on adaptive resistance evolution in GBM to therapy.
胶质母细胞瘤（GBM）是一种高度致命的癌症，普遍对手术切除、放疗和化疗的标准多模态治疗具有抗药性。替莫唑胺（TMZ）是目前治疗 GBM 的最佳化疗药物，但由于肿瘤耐药，其反应的持久性在表观遗传学上是依赖的，而且往往是短暂的。在 GBM 中，迫切需要能够与放化疗协同作用的治疗方法。有越来越多的证据表明，GBM 中的适应性耐药进化是通过治疗诱导的表观遗传修饰来促进的。DNA 甲基化、组蛋白修饰和染色质重塑的表观遗传改变都被认为是增强关键基因转录激活的机制，这些基因在 GBM 耐药性和致死性中发挥着关键作用。因此，了解和靶向与 GBM 耐药性相关的表观遗传修饰是当务之急。在这篇综述中，我们总结了最近关于表观遗传修饰对 GBM 对治疗的适应性耐药进化的影响的最新进展。
Zotero 插件