Review

Oncolytic herpes simplex virus vectors and chemotherapy: are combinatorial strategies more effective for cancer?

Brain Tumor Research Center, Department of Neurosurgery, Massachusetts General Hospital, & Harvard Medical School, Boston, MA, USA

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Hiroaki Wakimoto

Brain Tumor Research Center, Department of Neurosurgery, Massachusetts General Hospital, & Harvard Medical School, Boston, MA, USA

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Tooba Cheema

Brain Tumor Research Center, Department of Neurosurgery, Massachusetts General Hospital, & Harvard Medical School, Boston, MA, USA

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Samuel D Rabkin

† Author for correspondence

Brain Tumor Research Center, Department of Neurosurgery, Massachusetts General Hospital, & Harvard Medical School, Boston, MA, USA.

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Email the corresponding author at rabkin@helix.mgh.harvard.edu

Published Online:7 Apr 2010https://doi.org/10.2217/fon.10.18

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Abstract

>Despite aggressive treatments, including chemotherapy and radiotherapy, cancers often recur owing to resistance to conventional therapies. Oncolytic viruses such as oncolytic herpes simplex virus (oHSV) represent an exciting biological approach to cancer therapy. A range of viral mutations has been engineered into HSV to engender oncolytic activity. While oHSV as a single agent has been tested in a number of cancer clinical trials, preclinical studies have demonstrated enhanced efficacy when it is combined with cytotoxic anticancer drugs. Among the strategies that will be discussed in this article are combinations with standard-of-care chemotherapeutics, expression of prodrug-activating enzymes to enhance chemotherapy and small-molecule inhibitors. The combination of oHSV and chemotherapy can achieve much more efficient cancer cell killing than either single agent alone, often through synergistic interactions. This can be clinically important not just for improving efficacy but also for permitting lower and less toxic chemotherapeutic doses. The viral mutations in an oHSV vector often determine the favorability of its interactions with chemotherapy, just as different cancer cells, due to genetic alterations, vary in their response to chemotherapy. As chemotherapeutics are often the standard of care, combining them with an investigational new drug, such as oHSV, is clinically easier than combining multiple novel agents. As has become clear for most cancer therapies, multimodal treatments are usually more effective. In this article, we will discuss the recent progress of these combinatorial strategies between virotherapy and chemotherapy and future directions.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Acknowledgements

The authors would like to thank members of the Brain Tumor Research Center, past and present, who have contributed to our research and thinking, in particular Dr Robert Martuza.

Financial & competing interests disclosure

Our studies have been supported in part by grants from the National Institutes of Health and the Department of Defense. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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