Gene Therapy Strategy for Tumour Hypoxia

A characteristic feature of solid tumours is the presence of cells under very low oxygen tensions, hypoxia. These cells, so called hypoxic tumour cells, express a transcription factor, hypoxia-inducible factor 1 (HIF-1), which induces the expression of more than one hundred genes related to angiogenesis, invasion, metastasis, and resistance to conventional treatments such as chemotherapy and radiotherapy. However, because hypoxia is unique to locally advanced malignant tumours, it provides the opportunity to develop tumourspecific targeting strategies. Such an approach has been applied to gene therapy; for example, hypoxia-activated gene therapy using HIF-1-dependent promoters resulted in the selective expression of therapeutic genes and anti-tumour effects with minimum side effects in normal tissues. Here, I review recent advances in the development of cancer gene therapy strategies targeting hypoxic/HIF-1-active tumour cells.