PDF(Pubmed)
Abstract：
Glioblastoma, the most aggressive and common malignant primary brain tumour, is characterized by infiltrative growth, abundant vascularization, and aggressive clinical evolution. Patients with glioblastoma often face poor prognoses, with a median survival of approximately 15 months. Technological progress and the subsequent improvement in understanding the pathophysiology of these tumours have not translated into significant achievements in therapies or survival outcomes for patients. Progress in molecular profiling has yielded new omics data for a more refined classification of glioblastoma. Several typical genetic and epigenetic alterations in glioblastoma include mutations in genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, and retinoblastoma protein (RB) signalling, as well as mutation of isocitrate dehydrogenase (IDH), methylation of O6-methylguanine-DNA methyltransferase (MGMT), amplification of epidermal growth factor receptor vIII, and codeletion of 1p/19q. Certain microRNAs, such as miR-10b and miR-21, have also been identified as prognostic biomarkers. Effective treatment options for glioblastoma are limited. Surgery, radiotherapy, and alkylating agent chemotherapy remain the primary pillars of treatment. Only promoter methylation of the gene MGMT predicts the benefit from alkylating chemotherapy with temozolomide and it guides the choice of first-line treatment in elderly patients. Several targeted strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles are under investigation in clinical trials. This review explores the potential genetic and epigenetic biomarkers that could be deployed as analytical tools in the diagnosis and prognostication of glioblastoma. Recent clinical advancements in treating glioblastoma are also discussed, along with the potential of liquid biopsies to advance personalized medicine in the field of glioblastoma, highlighting the challenges and promises for the future.
摘要：
胶质母细胞瘤,最侵袭性和最常见的恶性原发性脑肿瘤，以渗透生长为特征，丰富的血管形成，和积极的临床进化。胶质母细胞瘤患者经常面临不良预后，中位生存期约为15个月。技术进步和随后对这些肿瘤的病理生理学理解的改进并没有转化为治疗或患者生存结果的重大成就。分子谱分析的进展为胶质母细胞瘤的更精细分类提供了新的组学数据。胶质母细胞瘤中几种典型的遗传和表观遗传改变包括调节受体酪氨酸激酶（RTK）/大鼠肉瘤（RAS）/磷酸肌醇3-激酶（PI3K）的基因突变，p53和视网膜母细胞瘤蛋白（RB）信号，以及异柠檬酸脱氢酶（IDH）的突变，O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的甲基化，表皮生长因子受体VIII的扩增，和共删除1p/19q。某些microRNAs,如miR-10b和miR-21，也已被确定为预后生物标志物。胶质母细胞瘤的有效治疗选择有限。手术,放射治疗,和烷化剂化疗仍然是治疗的主要支柱。MGMT基因的启动子甲基化可以预测替莫唑胺烷基化化疗的益处，并指导老年患者一线治疗的选择。在临床试验中正在研究基于肿瘤固有的显性信号传导途径和抗原肿瘤谱的几种靶向策略。这篇综述探讨了潜在的遗传和表观遗传生物标志物，可作为胶质母细胞瘤诊断和预后的分析工具。还讨论了胶质母细胞瘤治疗的最新临床进展，随着液体活检在胶质母细胞瘤领域推进个性化医疗的潜力，强调未来的挑战和承诺。
