Oncolytic viral therapy: targeting cancer stem cells.

IF 6.7 Oncolytic Virotherapy Pub Date : 2014-02-01 DOI:10.2147/OV.S52749
Tyrel T Smith, Justin C Roth, Gregory K Friedman, G Yancey Gillespie
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引用次数: 27

Abstract

Cancer stem cells (CSCs) are defined as rare populations of tumor-initiating cancer cells that are capable of both self-renewal and differentiation. Extensive research is currently underway to develop therapeutics that target CSCs for cancer therapy, due to their critical role in tumorigenesis, as well as their resistance to chemotherapy and radiotherapy. To this end, oncolytic viruses targeting unique CSC markers, signaling pathways, or the pro-tumor CSC niche offer promising potential as CSCs-destroying agents/therapeutics. We provide a summary of existing knowledge on the biology of CSCs, including their markers and their niche thought to comprise the tumor microenvironment, and then we provide a critical analysis of the potential for targeting CSCs with oncolytic viruses, including herpes simplex virus-1, adenovirus, measles virus, reovirus, and vaccinia virus. Specifically, we review current literature regarding first-generation oncolytic viruses with their innate ability to replicate in CSCs, as well as second-generation viruses engineered to enhance the oncolytic effect and CSC-targeting through transgene expression.

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溶瘤病毒治疗:靶向癌症干细胞。
癌症干细胞(Cancer stem cells, CSCs)被定义为具有自我更新和分化能力的罕见肿瘤起始癌细胞群。由于CSCs在肿瘤发生中的关键作用,以及它们对化疗和放疗的耐药性,目前正在进行广泛的研究,以开发针对CSCs的癌症治疗方法。为此,针对独特的CSC标记物、信号通路或促肿瘤CSC利基的溶瘤病毒作为CSC破坏剂/治疗方法具有很大的潜力。我们总结了CSCs的现有生物学知识,包括它们的标记物和被认为构成肿瘤微环境的生态位,然后我们对溶瘤病毒(包括单纯疱疹病毒-1、腺病毒、麻疹病毒、呼肠孤病毒和牛痘病毒)靶向CSCs的潜力进行了关键分析。具体来说,我们回顾了目前关于第一代溶瘤病毒的文献,这些病毒具有先天的在csc中复制的能力,以及第二代通过转基因表达来增强溶瘤效应和csc靶向性的病毒。
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The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment. Treatment of an Alveolar Rhabdomyosarcoma Allograft with Recombinant Myxoma Virus and Oclacitinib. Virus-Receptor Interactions and Virus Neutralization: Insights for Oncolytic Virus Development. Impact of Induced Syncytia Formation on the Oncolytic Potential of Myxoma Virus. Virus-Receptor Interactions: Structural Insights For Oncolytic Virus Development.
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