Primary CNS neoplasms of adults affect approximately 8.2/100,000 population annually in the USA (Walker et al, 1985). About half of these tumours are highly aggressive malignant gliomas, and are associated with a median survival of four to twelve months following diagnosis (Jubelirer, 1996; Lopez Gonzalez and Sotelo, 2000).
Treatment is palliative; despite recent advances in surgery, radiotherapy and chemotherapy, little impact has been made on the poor prognosis associated with this malignancy (West et al, 1983; Kelly et al, 1984; Jubelirer, 1996; Lang et al, 1999; Lopez Gonzalez and Sotelo, 2000). Exploration of novel treatment strategies is therefore of importance.
Cancer is a genetic disease (Collins, 1998; Hill et al, 1999; Hanahan and Weinberg, 2000), oncogenic mutations usually being acquired rather than inherited. Genetic intervention represents a valid and logical approach to developing novel anti-cancer therapeutics. Gliomas are attractive targets for delivery of therapeutic transgenes by genetically engineered vectors; the tumours are highly localised as, although they are usually invasive locally at the tumour margin (McComb and Bigner, 1984), they only metastasise under unusual circumstances (al Rikabi et al, 1997; Hsu et al, 1998). This enables direct inoculation of the tumour or post-operative tumour cavity with recombinant vector, circumventing many challenges currently associated with systemic transgene delivery.
In this review, we consider advances in the construction of herpes simplex-based gene therapy vectors, discuss the types of therapeutic transgenes whose deliver to tumours may be desirable, and review the results from pre-clinical experimental treatment trials using these approaches.
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