Targeting tumour angiogenesis with small molecule inhibitors of hypoxia inducible factor.

The adaptation of tumours to hypoxia is critical for their survival and growth. The high proliferation rate of solid tumours causes the continuous outstripping of the oxygen supply provided by the local vasculature, resulting in hypoxic regions within the tumour. Hypoxia inducible factor (HIF) is the key mediator of cellular response to hypoxia, activating the expression of multiple genes that participate in angiogenesis, iron metabolism, glycolysis, glucose transport and cell proliferation and survival. The critical role of the hypoxia response network and HIF in cancer has resulted in it being viewed as an ideal target for small molecule intervention. In this tutorial review we discuss the central role of HIF in the adaptation of tumours to a hypoxic environment, going on to describe recent attempts at developing small molecules that disrupt this pathway and their potential for use as the next generation anticancer therapeutics. This journal is © The Royal Society of Chemistry 2011