Center for Cancer and Blood Disorders, Phoenix Children's Hospital, 1919 E Thomas Road, Phoenix, AZ, 85016, USA,
Adv Exp Med Biol. 2014;804:259-83. doi: 10.1007/978-3-319-04843-7_14.
Since the first anecdotal reports of dramatic tumor responses following a viral infection in early 1900s, the field of oncolytic virotherapy has evolved at a rapid pace finally making its way into clinical trials. A large number of both wild-type and genetically altered viruses with a preferential replication-competency for tumor cells have been studied in tissue cultures, animal models and in humans, with an ever increasing repertoire of new viruses being added to this pool. Although oncolytic viruses have caused dramatic antitumor responses in cell cultures and mouse models, their clinical effects in humans have been modest. Therefore, the current research is focused on understanding the mechanisms by which viruses kill tumor cells, the barriers to successful viral delivery and penetration into tumor cells, the role of the immune system in viral oncolysis and generating stronger target specific and replication competent viruses. Osteosarcoma is a challenging malignancy to identify novel targets for therapy due to its complex genetic make-up. Oncolytic virotherapy may be a promising approach as a novel therapeutic, not dependent on consistent expression of a single target. In this review we summarize the supportive evidence and rationale for use of viral oncolysis in osteosarcoma along with the specific challenges it may face.
自 20 世纪初首次有报道称病毒感染后肿瘤出现明显缓解以来，溶瘤病毒治疗领域发展迅速，最终进入临床试验。大量野生型和基因改造型病毒在组织培养、动物模型和人体中进行了研究，不断有新的病毒加入到这一领域。尽管溶瘤病毒在细胞培养和小鼠模型中引起了明显的抗肿瘤反应，但在人体中的临床效果有限。因此，目前的研究集中在了解病毒杀伤肿瘤细胞的机制、成功将病毒递送到肿瘤细胞并穿透肿瘤细胞的障碍、免疫系统在病毒溶瘤中的作用以及生成更强的靶向特异性和复制能力的病毒。骨肉瘤的遗传构成复杂，因此确定新的治疗靶点具有挑战性。溶瘤病毒治疗可能是一种很有前途的治疗方法，它不依赖于单一靶标的持续表达。在本文综述中，我们总结了溶瘤病毒在骨肉瘤中的应用的支持证据和基本原理，以及它可能面临的具体挑战。
