Can gene therapy overcome the problem of hypoxia in radiotherapy?

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Abstract
Studies have shown that reduced oxygen tension (hypoxia) in solid tumours adversely affects the outcome of radiotherapy. Despite being an independent prognostic marker of poor treatment outcome, hypoxia represents a physiological difference that can be utilised for selective cancer treatment. Since severe hypoxia (pO2<0.3%; 2.5 mmHg) does not occur in normal tissue, it may be exploited for therapeutic gain. Accurate targeting of oxygen-deprived cells within a tumour mass may be achieved using hypoxia-targeted gene therapy. For gene therapy three separate issues need to be considered: 1) delivery of a gene to the tumour, 2) regulation of gene expression and 3) therapeutic efficacy. Each of these aspects is outlined here, with a view to gene therapy of the hypoxic tumour environment. It is proposed that by combining hypoxia-selective gene delivery with hypoxia-specific gene expression and oxygen-sensitive prodrug activation, radioresistant hypoxic tumour tissues may be effectively targeted.