A promising hypoxia-inducible suicide gene therapy strategy for prostate cancer

Abstract

Gene therapy targeted to hypoxic tumour cells may allow selective killing of malignant cells. The induction of gene expression under hypoxic conditions is governed by the activation of hypoxia-inducible factor 1 and its subsequent binding to hypoxia response elements. The HREs of a number of oxygen- responsive genes, including vascular endothelial growth factor (VEGF) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were cloned upstream of the cytosine deaminase (CD) gene. These constructs will drive the expression of this prodrug activation enzyme, which converts inactive 5- fluorocytosine (5-FC) to active 5-fluorouracil (5-FU), allowing selective killing of vector containing cells. 5-FU is also a radiosensitising agent, so specific expression of this agent in prostate cancer cells can also potentiate radiotherapy approaches in prostate cancer.