Garcia-Moure Marc, Martinez-Vélez Naiara, Patiño-García Ana, Alonso Marta M
The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.
Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.
J Bone Oncol. 2016 Dec 14;9:41-47. doi: 10.1016/j.jbo.2016.12.001. eCollection 2017 Nov.
Osteosarcoma is the most common bone cancer among those with non-hematological origin and affects mainly pediatric patients. In the last 50 years, refinements in surgical procedures, as well as the introduction of aggressive neoadjuvant and adjuvant chemotherapeutic cocktails, have increased to nearly 70% the survival rate of these patients. Despite the initial therapeutic progress the fight against osteosarcoma has not substantially improved during the last three decades, and almost 30% of the patients do not respond or recur after the standard treatment. For this group there is an urgent need to implement new therapeutic approaches. Oncolytic adenoviruses are conditionally replicative viruses engineered to selectively replicate in and kill tumor cells, while remaining quiescent in healthy cells. In the last years there have been multiple preclinical and clinical studies using these viruses as therapeutic agents in the treatment of a broad range of cancers, including osteosarcoma. In this review, we summarize some of the most relevant published literature about the use of oncolytic adenoviruses to treat human osteosarcoma tumors in subcutaneous, orthotopic and metastatic mouse models. In conclusion, up to date the preclinical studies with oncolytic adenoviruses have demonstrated that are safe and efficacious against local and metastatic osteosarcoma. Knowledge arising from phase I/II clinical trials with oncolytic adenoviruses in other tumors have shown the potential of viruses to awake the patient´s own immune system generating a response against the tumor. Generating osteosarcoma immune-competent adenoviruses friendly models will allow to better understand this potential. Future clinical trials with oncolytic adenoviruses for osteosarcoma tumors are warranted.
骨肉瘤是血液系统以外起源的最常见骨癌，主要影响儿童患者。在过去50年中，手术程序的改进以及积极的新辅助和辅助化疗方案的引入，使这些患者的生存率提高到了近70%。尽管在最初的治疗方面取得了进展，但在过去三十年中，对抗骨肉瘤的斗争并没有实质性改善，几乎30%的患者在标准治疗后没有反应或复发。对于这一群体，迫切需要实施新的治疗方法。溶瘤腺病毒是经过工程改造的条件性复制病毒，可在肿瘤细胞中选择性复制并杀死肿瘤细胞，而在健康细胞中保持静止。在过去几年中，有多项临床前和临床研究使用这些病毒作为治疗剂来治疗包括骨肉瘤在内的多种癌症。在这篇综述中，我们总结了一些关于使用溶瘤腺病毒在皮下、原位和转移性小鼠模型中治疗人类骨肉瘤肿瘤的最相关已发表文献。总之，迄今为止，溶瘤腺病毒的临床前研究表明，它们对局部和转移性骨肉瘤是安全有效的。在其他肿瘤中使用溶瘤腺病毒进行的I/II期临床试验所获得的知识表明，病毒有潜力唤醒患者自身的免疫系统，产生针对肿瘤的反应。建立骨肉瘤免疫活性腺病毒友好模型将有助于更好地理解这种潜力。未来有必要对骨肉瘤肿瘤进行溶瘤腺病毒的临床试验。
