Lab-03, Old Building, National Centre for Cell Science, Pune, India.
Department of Life Sciences, Shiv Nadar University, India.
Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188551. doi: 10.1016/j.bbcan.2021.188551. Epub 2021 Apr 20.
Glioblastoma is an incurable most prevalent primary malignant brain tumor in adults. Surgery followed by radiotherapy with concomitant chemotherapy is the standard of care in patients with glioblastoma. Although, prognosis remains poor with a median survival in the range of 12-15 months. Over the decades of research has identified the gene mutation, angiogenesis, cell signaling for the development novel therapeutics. However, recent understanding on extrachromosomal DNA (ecDNA) put extra-layer of complexity in glioblastoma pathogenesis. These ecDNAs are present in significantly higher copy number in the nucleus of the cancer cells and contains several oncogenes which are instrumental for intra-tumoral genetic heterogeneity, accelerated tumor evolution and therapy resistance. In this review, we will discuss the current understanding on biogenesis, disease progression and potential therapeutic implications of ecDNAs in glioblastoma.
胶质母细胞瘤是一种无法治愈的最常见的成人原发性恶性脑肿瘤。手术联合放化疗是胶质母细胞瘤患者的标准治疗方法。尽管中位生存期在 12-15 个月之间，但预后仍然很差。几十年来的研究已经确定了基因突变、血管生成、细胞信号转导，为开发新的治疗方法提供了依据。然而，最近对额外染色体 DNA（ecDNA）的理解为胶质母细胞瘤的发病机制增加了额外的复杂性。这些 ecDNA 在癌细胞的核内存在显著更高的拷贝数，并包含几个癌基因，这些癌基因对于肿瘤内遗传异质性、肿瘤加速进化和治疗耐药性至关重要。在这篇综述中，我们将讨论 ecDNA 在胶质母细胞瘤中的生物发生、疾病进展和潜在治疗意义的最新认识。
