The Institute of Cancer Research, Targeted Therapy Team, Chester Beatty Laboratories, London, UK.
Expert Opin Biol Ther. 2012 Dec;12(12):1669-78. doi: 10.1517/14712598.2012.745507.
Locally advanced head and neck cancer carries a poor prognosis, even with standard combination (surgery, radiotherapy, chemotherapy) treatment regimens. There is a pressing need for novel therapies with activity against this tumour type. Oncolytic reovirus type 3 (Dearing) is preferentially cytotoxic in tumour cells with an activated Ras signalling pathway and represents a promising novel therapy with relevance in head and neck cancer.
In this review, we discuss the pre-clinical and clinical data that have underpinned the translational development of oncolytic reovirus thus far. In particular, we describe the iterative nature of the research programme through initial studies testing single-agent reovirus therapy and on to subsequent work in which reovirus has been combined with either radiotherapy or cytotoxic chemotherapy. We will trace the process by which oncolytic reovirus has reached Phase III evaluation in combination with carboplatin/paclitaxel in patients with platin-refractory, relapsed/metastatic head and neck cancer.
Reovirus is a self-amplifying, cancer-selective agent that offers huge potential advantages over standard chemotherapy, targeted small molecules or monoclonal antibodies. However, it is most likely that reovirus will show efficacy and be approved in combination with standard modalities (cytotoxic chemotherapy or radiotherapy) or other targeted agents, especially those that modulate signal transduction pathways. The next 5 years are critical for the development of oncolytic reovirus as an anti-cancer therapy and hinge on the ongoing Phase III trial in head and neck cancer and other Phase II programmes.
局部晚期头颈部癌症即使采用标准联合（手术、放疗、化疗）治疗方案，预后仍较差。因此迫切需要针对这种肿瘤类型具有活性的新疗法。溶瘤性呼肠孤病毒 3 型（Dearing）对激活 Ras 信号通路的肿瘤细胞具有优先细胞毒性，是一种很有前途的新型疗法，对头颈部癌症具有相关性。
在这篇综述中，我们讨论了迄今为止支持溶瘤性呼肠孤病毒转化研究发展的临床前和临床数据。特别是，我们描述了研究计划的迭代性质，最初的研究测试了单药治疗的溶瘤性呼肠孤病毒疗法，然后是将呼肠孤病毒与放疗或细胞毒性化疗联合使用的后续工作。我们将追溯溶瘤性呼肠孤病毒与卡铂/紫杉醇联合用于铂类耐药、复发性/转移性头颈部癌症患者的 III 期评估的过程。
呼肠孤病毒是一种自我扩增的、选择性针对癌症的药物，与标准化疗、靶向小分子药物或单克隆抗体相比，具有巨大的潜在优势。然而，呼肠孤病毒最有可能与标准治疗方式（细胞毒性化疗或放疗）或其他靶向药物联合显示疗效并获得批准，尤其是那些调节信号转导途径的药物。未来 5 年是开发溶瘤性呼肠孤病毒作为抗癌疗法的关键时期，这取决于头颈部癌症的 III 期临床试验和其他 II 期计划。
