The clinical management of cancer continues to be dominated by macroscopic surgical resection, radiotherapy, and cytotoxic drugs. The major challenge facing oncology is to achieve more selective, less toxic and effective methods of targeting disseminated tumors, a challenge oncolytic virotherapy may be well-placed to meet. Characterization of coxsackievirus A21 (CVA21) receptor-based mechanism of virus internalization and lysis in the last decade has suggested promise for CVA21 as a virotherapy against malignancies which overexpress those receptors. Preclinical studies have demonstrated proof of principle, and with the results of early clinical trials awaited, CVA21 may be one of the few viruses to demonstrate benefit for patients. This review outlines the potential of CVA21 as an oncolytic agent, describing the therapeutic development of CVA21 in preclinical studies and early stage clinical trials. Preclinical evidence supports the potential use of CVA21 across a range of malignancies. Malignant melanoma is the most intensively studied cancer, and may represent a “test case” for future development of the virus. Although there are theoretical barriers to the clinical utility of oncolytic viruses like CVA21, whether these will block the efficacy of the virus in clinical practice remains to be established, and is a question which can only be answered by appropriate trials. As these data become available, the rapid journey of CVA21 from animal studies to clinical trials may offer a model for the translation of other oncolytic virotherapies from laboratory to clinic
