ReviewOncolytic viruses in radiation oncology
Section snippets
Principles of viral therapies in oncology
Viruses have been widely studied as vectors for therapeutic genes. Gene therapy consists of the introduction of genetic material into cells for a therapeutic purpose. Recombinant viruses have been shown to be an efficient means of achieving gene transfer both in vitro and in vivo. Many viruses, such as adenovirus, adeno-associated virus (AAV), retrovirus, lentivirus, herpes simplex virus (HSV), poxvirus, measles virus, simian virus 40 recombinant (SV40r) and vesicular stomatitis virus have been
Antitumour activity
Antitumour activities in vitro and in vivo of various viral agents in combination with EBRT have been investigated in a variety of tumour models. The combination of viruses and EBRT has shown additive or synergistic therapeutic effects in vitro and in subcutaneous prostate, head and neck, lung, colon, thyroid and cholangiocarcinomas, as well as melanoma and malignant glioma [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25].
In
DNA damage signalling
Ionizing radiation produces a wide variety of lesions in DNA, including base damage, single- and double-strand breaks (DSB) and DNA–DNA or DNA–protein crosslinks [54]. These lesions can be topographically grouped and clustered within the same region of DNA to comprise so-called “complex damage” [55]. DSBs breaks play an important role in cell death induced by radiation. Two major mechanisms of repair of DSBs have been described: the non-homologous end-joining (NHEJ) mechanisms and homologous
Conclusion
Viral therapies are unlikely to be used widely in the clinic as single agents. However, it is increasingly recognized that combining viral therapies with EBRT represents a promising approach. Preclinical studies support this strategy showing that combination regimens yield increased antitumour effects as compared with single treatment modalities. A number of potential mechanisms of interaction between viruses and radiation have been described. Radiation can increase viral uptake, gene
Authors’ declaration of personal interests
K.J. Harrington has received unrestricted educational grants in support of laboratory and clinical research from Oncolytics Biotech Inc. and Genelux GmbH.
Acknowledgements
Y. Touchefeu has received a doctoral research grant from the Institut National du Cancer and a research grant from the Société Nationale Française de Gastro-Entérologie (Robert Tournut grant). Part of this work was undertaken in The Royal Marsden NHS Foundation Trust who received a proportion of its funding from the NHS Executive; the views expressed in this publication are those of the authors and not necessarily those of the NHS Executive. This work was supported by The Institute of Cancer
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