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当前 LNA-抗-miR 寡核苷酸和 microRNA miR-21 抑制剂在结直肠癌治疗中作为一种潜在治疗选择的现状和展望。

Current Status and Perspectives Regarding LNA-Anti-miR Oligonucleotides and microRNA miR-21 Inhibitors as a Potential Therapeutic Option in Treatment of Colorectal Cancer.

机构信息

Deputy of Food and Drug, Isfahan University of Medical Sciences, Isfahan, Iran.

Student Research Committee, Department of medical biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Cell Biochem. 2017 Dec;118(12):4129-4140. doi: 10.1002/jcb.26047. Epub 2017 May 23.

Abstract

Colorectal cancer (CRC) is among the leading causes of cancer-related death, principally due to its metastatic spread and multifactorial chemoresistance. The therapeutic failure can also be explained by inter- or intra-tumor genetic heterogeneity and tumor stromal content. Thus, the identification of novel prognostic biomarkers and therapeutic options are warranted in the management of CRC patients. There are data showing that microRNA-21 is elevated in different types of cancer, particularly colon adenocarcinoma and that this is association with a poor prognosis. This suggests that microRNA-21 may be of value as a potential therapeutic target. Furthermore, locked nucleic acid (LNA)-modified oligonucleotides have recently emerged as a therapeutic option for targeting dysregulated miRNAs in cancer therapy, through antisense-based gene silencing. Further work is required to identify innovative anticancer drugs that improve the current therapy either through novel combinatorial approaches or with better efficacy than conventional drugs. We aimed to provide an overview of the preclinical and clinical studies targeting key dysregulated signaling pathways in CRC as well as the therapeutic application of LNA-modified oligonucleotides, and miR inhibitors in the treatment of CRC patients. J. Cell. Biochem. 118: 4129-4140, 2017. © 2017 Wiley Periodicals, Inc.

摘要

结直肠癌(CRC)是癌症相关死亡的主要原因之一,主要是由于其转移扩散和多因素化学耐药性。治疗失败也可以解释为肿瘤内或肿瘤间遗传异质性和肿瘤基质含量。因此,有必要在 CRC 患者的管理中确定新的预后生物标志物和治疗选择。有数据表明,microRNA-21 在不同类型的癌症中升高,特别是结肠腺癌,并且与预后不良相关。这表明 microRNA-21 可能作为一种潜在的治疗靶点具有价值。此外,锁核酸(LNA)修饰的寡核苷酸最近作为癌症治疗中靶向失调 miRNA 的治疗选择出现,通过基于反义的基因沉默。需要进一步的工作来确定创新的抗癌药物,通过新的组合方法或比传统药物更好的疗效来改善当前的治疗。我们旨在提供针对 CRC 中关键失调信号通路的临床前和临床研究以及 LNA 修饰的寡核苷酸和 miR 抑制剂在 CRC 患者治疗中的治疗应用的概述。J. Cell. Biochem. 118: 4129-4140, 2017. © 2017 Wiley Periodicals, Inc.

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