研究概要
结直肠癌(CRC)是全球癌症相关发病率和死亡率的主要原因之一,大多数患者,尤其是微卫星稳定型患者,治疗选择有限。
中文摘要
结直肠癌(CRC)是全球癌症相关发病率和死亡率的主要原因之一,大多数患者,尤其是微卫星稳定型患者,治疗选择有限。溶瘤病毒(OVs)因其能够选择性在恶性细胞中复制,并通过直接溶瘤、免疫激活和调节肿瘤血管生成介导抗肿瘤效应,已成为一种有前景的治疗方式。本综述分析了101项报告使用OV治疗CRC的原始研究。提取的数据,包括病毒类型、研究设计、模型系统、机制通路和治疗策略,被归纳为单独治疗、联合治疗或基于增强剂的策略。在所有研究中,OV单一治疗一致性地诱导选择性肿瘤细胞裂解,并在某些模型中还表现出额外的免疫原性和抗血管生成效应。联合策略,特别是与免疫检查点抑制剂联合,表现出协同活性,即使在耐药CRC环境中也能增强T细胞浸润、细胞因子产生和肿瘤控制。增强剂策略,包括间充质干细胞递送系统和肿瘤特异性启动子,改善了病毒选择性、肿瘤穿透性并减少了免疫清除。尽管研究结果令人鼓舞,但进展受到模型异质性和晚期临床试验稀缺的阻碍。目前有必要转化为设计良好的临床研究,以优化治疗结果。
展开英文摘要原文
Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide, with most patients, especially those with microsatellite-stable disease, having limited treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic modality due to their ability to selectively replicate in malignant cells and mediate antitumor effects through direct oncolysis, immune activation, and modulation of tumor angiogenesis. This review analyzed 101 primary studies that reported the use of OV in CRC. The extracted data, including virus type, study design, model system, mechanistic pathways, and therapeutic strategies, were organized as standalone therapy, combination therapy, or enhancer-based approaches. Across studies, OV monotherapy consistently induced selective tumor cell lysis and, in some models, also exhibited additional immunogenic and anti-angiogenic effects. Combination strategies, particularly those with immune checkpoint inhibitors, demonstrated synergistic activity, enhancing T-cell infiltration, cytokine production, and tumor control even in resistant CRC settings. Enhancer approaches, including mesenchymal stem cell delivery systems and tumor-specific promoters, have improved viral selectivity, tumor penetration, and reduced immune clearance. Despite promising findings, progress is hindered by heterogeneous models and the scarcity of advanced clinical trials. Translation into well-designed clinical studies is now warranted to optimize therapeutic outcomes.
论文信息
- 作者
- Salameh H、Naseem N、Chattha MA、Ramesh J、Ramy H、Cizkova D、Kubatka P、Büsselberg D
- 单位
- Weill Cornell Medicine-Qatar, Cornell University, Doha P.O. Box 24144, Qatar.
- 文献类型
- 综述 · 非美国政府资助研究
- 期刊
- Cells2025 Dec 16