Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic approaches. Oncolytic treatments, particularly oncolytic viruses (OVs), have emerged as promising candidates by selectively infecting and lysing tumor cells while stimulating anti-tumor immunity. Various virus-based therapies are under investigation, including genetically engineered herpes simplex virus (HSV), adenovirus, poliovirus, reovirus, vaccinia virus, measles virus, and Newcastle disease virus, each exploiting unique tumor-selective mechanisms. While some, such as HSV-based therapies including G207 and DelytactTM, have demonstrated clinical progress, significant challenges persist, including immune evasion, heterogeneity in patient response, and delivery barriers due to the blood–brain barrier. Moreover, combination strategies integrating OVs with immune checkpoint inhibitors, chemotherapy, and radiation are promising but require further clinical validation. Non-viral oncolytic approaches, such as tumor-targeting bacteria and synthetic peptides, remain underexplored. This review highlights current advancements while addressing critical gaps in the literature, including the need for optimized delivery methods, better biomarker-based patient stratification, and a deeper understanding of GBM’s immunosuppressive microenvironment. Future research should focus on enhancing OV specificity, engineering viruses to deliver therapeutic genes, and integrating OVs with precision medicine strategies. By identifying these gaps, this review provides a framework for advancing oncolytic therapies in GBM treatment.
胶质母细胞瘤（GBM）作为最具侵袭性且治疗抵抗性最强的脑肿瘤之一，亟需开发新型治疗策略。溶瘤疗法，特别是溶瘤病毒，通过选择性感染并裂解肿瘤细胞，同时激发抗肿瘤免疫反应，已成为极具前景的治疗方向。目前多种基于病毒的疗法正处于研究阶段，包括基因工程改造的单纯疱疹病毒、腺病毒、脊髓灰质炎病毒、呼肠孤病毒、痘苗病毒、麻疹病毒及新城疫病毒，这些病毒各自利用独特的肿瘤选择性机制发挥作用。尽管以单纯疱疹病毒为基础的疗法（如G207和DelytactTM）已取得临床进展，但仍面临诸多挑战，包括肿瘤免疫逃逸、患者反应异质性以及血脑屏障导致的递送障碍。此外，将溶瘤病毒与免疫检查点抑制剂、化疗及放疗相结合的联合策略展现出潜力，但尚需进一步的临床验证。非病毒溶瘤方法（如靶向肿瘤的细菌疗法和合成多肽疗法）的研究仍显不足。本综述系统梳理了当前研究进展，同时指出该领域的关键空白，包括优化递送方法、建立基于生物标志物的患者分层体系，以及深化对GBM免疫抑制微环境的理解。未来研究应聚焦于提升溶瘤病毒特异性、设计携带治疗基因的工程化病毒，并将溶瘤疗法与精准医疗策略相整合。通过明确这些研究方向，本综述为推进溶瘤疗法在GBM治疗中的应用提供了理论框架。
Oncolytic Therapies for Glioblastoma: Advances, Challenges, and Future Perspectives
肿瘤(癌症)患者之家