Telomerase inhibition in malignant gliomas: a systematic review.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Quintino Giorgio D'Alessandris, Marco Battistelli, Giovanni Pennisi, Martina Offi, Maurizio Martini, Tonia Cenci, Maria Laura Falchetti, Liverana Lauretti, Alessandro Olivi, Roberto Pallini, Nicola Montano
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引用次数: 1

Abstract

Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in in vitro and in vivo settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.

端粒酶抑制在恶性胶质瘤中的作用:一项系统综述。
胶质母细胞瘤(GBM)是最常见的成人恶性脑肿瘤,尽管治疗方法不同,但中位总生存期仍在14至18个月之间。因此,迫切需要新的治疗策略。然而,由于这种肿瘤在组织病理、分子、遗传和表观遗传特征方面的高度异质性,在GBM中确定癌症特异性靶点尤其具有挑战性。端粒酶再激活是恶性胶质瘤的标志。编码端粒酶活性亚基的hTERT基因的激活突变是2021年世卫组织中枢神经系统肿瘤分类中确定GBM (IDH-wildtype)诊断的分子标准之一。因此,端粒酶抑制至少在理论上代表了一种有希望的GBM治疗策略:药物化合物以及直接基因表达调节疗法已经成功地应用于体外和体内环境。不幸的是,端粒酶抑制在GBM中的临床应用目前很少。本系统综述的目的是提供端粒酶抑制作为恶性胶质瘤治疗策略的最新研究报告,以促进该主题的未来转化和临床研究。
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来源期刊
Expert Reviews in Molecular Medicine
Expert Reviews in Molecular Medicine BIOCHEMISTRY & MOLECULAR BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.40
自引率
1.60%
发文量
45
期刊介绍: Expert Reviews in Molecular Medicine is an innovative online journal featuring authoritative and timely Reviews covering gene therapy, immunotherapeutics, drug design, vaccines, genetic testing, pathogenesis, microbiology, genomics, molecular epidemiology and diagnostic techniques. We especially welcome reviews on translational aspects of molecular medicine, particularly those related to the application of new understanding of the molecular basis of disease to experimental medicine and clinical practice.
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