Oncolytic reovirus type 3 (Dearing) as a novel therapy in head and neck cancer
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Introduction: 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. Areas covered: 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. Expert opinion: 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 anticancer therapy and hinge on the ongoing Phase III trial in head and neck cancer and other Phase II programmes.
head and neck cancer oncolytic virus ras pathway reovirus targeted therapy phase-i trial hepatocellular-carcinoma intravenous delivery chemotherapy poxvirus tumors cyclophosphamide radiotherapy combination efficacy
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EXPERT OPINION ON BIOLOGICAL THERAPY, 2012, 12 (12), pp. 1669 - 1678