Solid tumours differ in their physiology and microenvironment from normal tissue. They contain regions of chronic and transient hypoxia due to a chaotic vascular system.
Hypoxic cells are resistant to radiotherapy and often to chemotherapy.
We therefore aim to use gene therapy to specifically target this resistant subpopulation of cells, including both tumour and endothelial cells. Hypoxic cells are known to have a reduced metabolic rate, reduced transcription and translation, and often show a cell cycle arrest. We therefore needed to establish the feasibility of delivering DNA under tumour conditions. Current work involves the replacement of the marker gene in the hypoxia-responsive DNA constructs with therapeutic genes. The therapeutic genes under investigation encode plant and bacterial enzymes for their use in gene directed enzyme prodrug therapy.