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从 bench 到 bedside,小儿胶质瘤溶瘤病毒疗法的现状

From Bench to Bedside, the Current State of Oncolytic Virotherapy in Pediatric Glioma.

作者信息

Soldozy Sauson, Skaff Anthony, Soldozy Kamron, Sokolowski Jennifer D, Norat Pedro, Yagmurlu Kaan, Sharifi Khadijeh A, Tvrdik Petr, Park Min S, Kalani M Yashar S, Jane John A, Syed Hasan R

机构信息

Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Deparment of Neuroscience, University of Virginia Health System, Charlottesville, Virginia.

出版信息

Neurosurgery. 2020 Nov 16;87(6):1091-1097. doi: 10.1093/neuros/nyaa247.

Abstract

Glioma continues to be a challenging disease process, making up the most common tumor type within the pediatric population. While low-grade gliomas are typically amenable to surgical resection, higher grade gliomas often require additional radiotherapy in conjunction with adjuvant chemotherapy. Molecular profiling of these lesions has led to the development of various pharmacologic and immunologic agents, although these modalities are not without great systemic toxicity. In addition, the molecular biology of adult glioma and pediatric glioma has been shown to differ substantially, making the application of current chemotherapies dubious in children and adolescents. For this reason, therapies with high tumor specificity based on pediatric tumor cell biology that spare healthy tissue are needed. Oncolytic virotherapy serves to fill this niche, as evidenced by renewed interest in this domain of cancer therapy. Initially discovered by chance in the early 20th century, virotherapy has emerged as a viable treatment option. With promising results based on preclinical studies, the authors review several oncolytic viruses, with a focus on molecular mechanism and efficacy of these viruses in tumor cell lines and murine models. In addition, current phase I clinical trials evaluating oncolytic virotherapy in the treatment of pediatric glioma are summarized.

摘要

胶质瘤仍然是一个具有挑战性的疾病过程,是儿童群体中最常见的肿瘤类型。虽然低级别胶质瘤通常适合手术切除,但高级别胶质瘤往往需要联合辅助化疗进行额外的放疗。对这些病变的分子分析已促成了各种药理和免疫制剂的开发,尽管这些方法并非没有严重的全身毒性。此外,已表明成人胶质瘤和儿童胶质瘤的分子生物学有很大差异,这使得目前的化疗在儿童和青少年中的应用存在疑问。因此,需要基于儿童肿瘤细胞生物学且能保护健康组织的高肿瘤特异性疗法。溶瘤病毒疗法正好填补了这一空白,这一癌症治疗领域重新引起的关注就证明了这一点。溶瘤病毒疗法最初于20世纪初偶然发现,并已成为一种可行的治疗选择。基于临床前研究取得了有前景的结果,作者回顾了几种溶瘤病毒,重点是这些病毒在肿瘤细胞系和小鼠模型中的分子机制和疗效。此外,还总结了目前评估溶瘤病毒疗法治疗儿童胶质瘤的I期临床试验。

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