School of Medicine, University of Central Lancashire, Preston PR1 2HE, UK.
Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
Biochem Pharmacol. 2022 Jul;201:115090. doi: 10.1016/j.bcp.2022.115090. Epub 2022 May 14.
Glioma is the most common intracranial tumor with poor treatment outcomes and has high morbidity and mortality. Various studies on genomic analyses of glioma found a variety of deregulated genes with somatic mutations including TERT, TP53, IDH1, ATRX, TTN, etc. The genetic alterations in the key genes have been demonstrated to play a crucial role in gliomagenesis by modulating important signaling pathways that alter the fundamental intracellular functions such as DNA damage and repair, cell proliferation, metabolism, growth, wound healing, motility, etc. The SPRK1, MMP2, MMP9, AKT, mTOR, etc., genes, and noncoding RNAs (miRNAs, lncRNAs, circRNAs, etc.) were shown mostly to be implicated in the metastases of glioma. Despite advances in the current treatment strategies, a low-grade glioma is a uniformly fatal disease with overall median survival of ∼ 5-7 years while the patients bearing high-grade tumors display poorer median survival of ∼ 9-10 months mainly due to aggressive metastasis and therapeutic resistance. This review discusses the spectrum of deregulated genes, molecular and cellular mechanisms of metastasis, recurrence, and its management, the plausible causes for the development of therapy resistance, current treatment options, and the recent trends in malignant gliomas. Understanding the pathogenic mechanisms and advances in molecular genetics would aid in the novel diagnosis, prognosis, and translation of pathogenesis-based treatment opportunities which could pave the way for precision medicine in glioma.
神经胶质瘤是最常见的颅内肿瘤，治疗效果差，发病率和死亡率高。各种关于神经胶质瘤基因组分析的研究发现了多种失调基因，包括 TERT、TP53、IDH1、ATRX、TTN 等，体细胞突变。关键基因的遗传改变已被证明通过调节重要的信号通路在神经胶质瘤发生中起关键作用，这些信号通路改变了细胞内的基本功能，如 DNA 损伤和修复、细胞增殖、代谢、生长、伤口愈合、运动等。SPRK1、MMP2、MMP9、AKT、mTOR 等基因和非编码 RNA（miRNAs、lncRNAs、circRNAs 等）主要与神经胶质瘤的转移有关。尽管目前的治疗策略有所进展，但低级别神经胶质瘤是一种普遍致命的疾病，总体中位生存期约为 5-7 年，而患有高级别肿瘤的患者中位生存期更差，约为 9-10 个月，主要是由于侵袭性转移和治疗耐药。这篇综述讨论了失调基因、转移、复发的分子和细胞机制及其管理、治疗耐药发展的可能原因、当前的治疗选择以及恶性神经胶质瘤的最新趋势。了解发病机制和分子遗传学的进展将有助于为新的诊断、预后和基于发病机制的治疗机会提供帮助，为神经胶质瘤的精准医学铺平道路。
