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Oncolytic viral therapy: targeting cancer stem cells

机译:溶瘤病毒疗法:靶向癌症干细胞

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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.
机译:摘要:癌症干细胞(CSCs)被定义为能够自我更新和分化的稀有肿瘤引发癌细胞。由于其在肿瘤发生中的关键作用以及对化学疗法和放射疗法的抵抗力,目前正在进行广泛的研究以开发针对癌症治疗的CSC的疗法。为此,靶向独特的CSC标记,信号传导途径或肿瘤前CSC利基的溶瘤病毒具有作为CSC破坏剂/治疗剂的潜力。我们提供了有关CSC生物学的现有知识的摘要,包括它们的标记和被认为构成肿瘤微环境的利基,然后我们对溶瘤病毒(包括单纯疱疹病毒1)靶向CSC的潜力进行了批判性分析,腺病毒,麻疹病毒,呼肠孤病毒和牛痘病毒。具体而言,我们回顾了有关第一代溶瘤病毒及其在CSC中复制的先天能力的最新文献,以及经过工程改造以通过转基因表达增强溶瘤作用和CSC靶向的第二代病毒。

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