University of Athens, Medical School, Department of Biological Chemistry, Athens, Greece.
Expert Opin Investig Drugs. 2012 Oct;21(10):1475-88. doi: 10.1517/13543784.2012.710199. Epub 2012 Jul 19.
Gliomas consist of a very heterogeneous group of malignant tumors, accounting for 50 - 60% of primary brain tumors. Despite all the efforts of cytoreductive surgery in combination with intense chemoradiotherapy, glioblastoma multiforme (GBM, glioma grade IV) still has a dismal prognosis. Current research is focused on molecular targeting to overcome resistance to conventional therapy. MicroRNAs (miRNAs), small non-coding RNAs, represent endogenous agents of RNA interference, dramatically changing expression of target proteins. Their role in brain physiology as well as GBM development has attracted intense research efforts pointing toward therapeutic potential and immediate targeting for sensitization of glioma cells to chemo and/or radiotherapy.
This review is focused on the variable role of miRNAs in gliomagenesis and their possible clinical relevance in patient's survival and prognosis. It further addresses the potential application of selected miRNAs as therapeutic targets or agents in GMB, including data from clinical studies in other central nervous system tumors.
Although miRNA-targeted therapy is still in its initial stage and clinical trials with glioma/brain tumor patients are under recruitment or currently running, several miRNAs have been selected as promising tumor biomarkers, with increased potential to reduce disease progression in combination to conventional first-line therapy for gliomas.
神经胶质瘤由一组非常异质的恶性肿瘤组成,占原发性脑肿瘤的 50-60%。尽管进行了最大限度的减瘤手术,并结合了强烈的化疗和放疗,多形性胶质母细胞瘤(GBM,IV 级胶质瘤)的预后仍然很差。目前的研究集中在分子靶向治疗以克服对常规治疗的耐药性。微小 RNA(miRNA)是小的非编码 RNA,是 RNA 干扰的内源性调节剂,可显著改变靶蛋白的表达。它们在脑生理学以及 GBM 发展中的作用引起了人们的广泛关注,为治疗潜力和使胶质瘤细胞对化疗和/或放疗敏感的直接靶向提供了依据。
这篇综述主要讨论了 miRNA 在神经胶质瘤发生中的可变作用,以及它们在患者生存和预后中的可能临床相关性。它进一步探讨了选择 miRNA 作为治疗靶点或治疗剂在 GMB 中的潜在应用,包括来自其他中枢神经系统肿瘤的临床研究数据。
尽管 miRNA 靶向治疗仍处于起步阶段,针对胶质瘤/脑肿瘤患者的临床试验正在招募或正在进行中,但已有几种 miRNA 被选为有前途的肿瘤生物标志物,与传统一线治疗相结合,有更大潜力减少疾病进展。