Abstract:
Pediatric brain tumors are the most common solid tumors in children. Even to date, with the advances in multimodality therapeutic management, survival outcomes remain dismal in some types of tumors, such as pediatric-type diffuse high-grade gliomas or central nervous system (CNS) embryonal tumors. Failure to understand the complex molecular heterogeneity and the elusive tumor and microenvironment interplay continues to undermine therapeutic efficacy. Developing a strategy that would improve survival for these fatal tumors remains unmet in pediatric neuro-oncology. Oncolytic viruses (OVs) are emerging as a feasible, safe, and promising therapy for brain tumors. The new paradigm in virotherapy implies that the direct cytopathic effect is followed, under certain circumstances, by an antitumor immune response responsible for the partial or complete debulking of the tumor mass. OVs alone or combined with other therapeutic modalities have been primarily used in adult neuro-oncology. A surge in encouraging preclinical studies in pediatric brain tumor models recently led to the clinical translation of OVs with encouraging results in these tumors. In this review, we summarize the different virotherapy tested in preclinical and clinical studies in pediatric brain tumors, and we discuss the limitations and future avenues necessary to improve the response of these tumors to this type of therapy.
摘要:
小儿脑肿瘤是儿童中最常见的实体瘤。即使到目前为止,随着多模态治疗管理的进步,在某些类型的肿瘤中,生存结果仍然令人沮丧,如小儿型弥漫性高级别胶质瘤或中枢神经系统(CNS)胚胎性肿瘤。未能理解复杂的分子异质性以及难以捉摸的肿瘤和微环境相互作用继续破坏治疗功效。在儿科神经肿瘤学中,开发一种改善这些致命肿瘤生存率的策略仍未实现。溶瘤病毒(OVs)正在成为一种可行的病毒,安全,和有希望的治疗脑肿瘤。病毒疗法的新范式意味着遵循直接的细胞病变效应,在某些情况下,通过抗肿瘤免疫反应来部分或完全消除肿瘤块。OVs单独或与其他治疗方式组合已主要用于成人神经肿瘤学。最近,儿科脑肿瘤模型中令人鼓舞的临床前研究激增,导致OVs的临床转化,并在这些肿瘤中取得了令人鼓舞的结果。在这次审查中,我们总结了在小儿脑肿瘤的临床前和临床研究中测试的不同病毒疗法,我们讨论了改善这些肿瘤对这种治疗的反应所必需的局限性和未来的途径。