Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
Front Oncol. 2014 Jun 26;4:167. doi: 10.3389/fonc.2014.00167. eCollection 2014.
The development of wild-type, unmodified Type 3 Dearing strain reovirus as an anticancer agent has currently expanded to 32 clinical trials (both completed and ongoing) involving reovirus in the treatment of cancer. It has been more than 30 years since the potential of reovirus as an anticancer agent was first identified in studies that demonstrated the preferential replication of reovirus in transformed cell lines but not in normal cells. Later investigations have revealed the involvement of activated Ras signaling pathways (both upstream and downstream) and key steps of the reovirus infectious cycle in promoting preferential replication in cancer cells with reovirus-induced cancer cell death occurring through necrotic, apoptotic, and autophagic pathways. There is increasing evidence that reovirus-induced antitumor immunity involving both innate and adaptive responses also contributes to therapeutic efficacy though this discussion is beyond the scope of this article. Here, we review our current understanding of the mechanism of oncolysis contributing to the broad anticancer activity of reovirus. Further understanding of reovirus oncolysis is critical in enhancing the clinical development and efficacy of reovirus.
野生型、未经修饰的 3 型 Dearing 株呼肠孤病毒作为抗癌药物的开发目前已扩展到 32 项临床试验（包括已完成和正在进行的临床试验），涉及呼肠孤病毒治疗癌症。自从首次在研究中发现呼肠孤病毒作为抗癌药物的潜力以来，已经过去了 30 多年，这些研究表明呼肠孤病毒在转化细胞系中的复制具有优先性，但在正常细胞中则没有。后来的研究揭示了激活的 Ras 信号通路（上游和下游）以及呼肠孤病毒感染周期的关键步骤在促进癌细胞中的优先复制方面的作用，呼肠孤病毒诱导的癌细胞死亡是通过坏死、凋亡和自噬途径发生的。越来越多的证据表明，呼肠孤病毒诱导的抗肿瘤免疫反应，包括先天免疫和适应性免疫反应，也有助于治疗效果，尽管这一讨论超出了本文的范围。在这里，我们回顾了我们目前对溶瘤作用机制的理解，该机制有助于呼肠孤病毒的广泛抗癌活性。进一步了解呼肠孤病毒的溶瘤作用对于增强呼肠孤病毒的临床开发和疗效至关重要。
