Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Department of Gastroenterology, Nagoya City West Medical Center, Kita-Ku, Nagoya 467-8601, Japan.
Viruses. 2018 Aug 11;10(8):421. doi: 10.3390/v10080421.
Oncolytic viruses show intriguing potential as cancer therapeutic agents. These viruses are capable of selectively targeting and killing cancerous cells while leaving healthy cells largely unaffected. The use of oncolytic viruses for cancer treatments in selected circumstances has recently been approved by the Food and Drug Administration (FDA) of the US and work is progressing on engineering viral vectors for enhanced selectivity, efficacy and safety. However, a better fundamental understanding of tumour and viral biology is essential for the continued advancement of the oncolytic field. This knowledge will not only help to engineer more potent and effective viruses but may also contribute to the identification of biomarkers that can determine which patients will benefit most from this treatment. A mechanistic understanding of the overlapping activity of viral and standard chemotherapeutics will enable the development of better combinational approaches to improve patient outcomes. In this review, we will examine each of the factors that contribute to productive viral infections in cancerous cells versus healthy cells. Special attention will be paid to reovirus as it is a well-studied virus and the only wild-type virus to have received orphan drug designation by the FDA. Although considerable insight into reoviral biology exists, there remain numerous deficiencies in our understanding of the factors regulating its successful oncolytic infection. Here we will discuss what is known to regulate infection as well as speculate about potential new mechanisms that may enhance successful replication. A joint appreciation of both tumour and viral biology will drive innovation for the next generation of reoviral mediated oncolytic therapy.
溶瘤病毒作为癌症治疗药物具有引人注目的潜力。这些病毒能够选择性地靶向和杀死癌细胞，而对健康细胞的影响很小。溶瘤病毒在某些情况下用于癌症治疗已被美国食品和药物管理局 (FDA) 批准，并且正在努力设计具有增强的选择性、疗效和安全性的病毒载体。然而，为了继续推进溶瘤领域的发展，需要更好地理解肿瘤和病毒生物学。这种知识不仅有助于设计更有效和有效的病毒，还可能有助于确定哪些患者将从这种治疗中受益最大的生物标志物的鉴定。对病毒和标准化疗药物重叠活性的机制理解将能够开发出更好的联合方法来改善患者的治疗效果。在这篇综述中，我们将检查导致病毒在癌细胞和健康细胞中有效感染的每个因素。特别关注呼肠孤病毒，因为它是一种研究充分的病毒，也是唯一一种被 FDA 授予孤儿药指定的野生型病毒。尽管对呼肠孤病毒生物学有了相当多的了解，但我们对调节其成功溶瘤感染的因素的理解仍存在许多不足。在这里，我们将讨论已知的调节感染的因素，并推测可能增强成功复制的潜在新机制。对肿瘤和病毒生物学的共同理解将推动下一代基于呼肠孤病毒的溶瘤治疗的创新。
