Development of novel therapeutic strategies that target HIF-1.

Activity of hypoxia-inducible factor 1 (HIF-1) is increased in human cancers as a result of the physiological induction of HIF-1alpha in response to intratumoural hypoxia and as a result of genetic alterations that activate oncogenes and inactivate tumour suppressor genes. In many cancer types, increased HIF-1alpha expression is associated with increased risk of patient mortality. HIF-1 plays important roles in every major aspect of cancer biology through the transcriptional regulation of hundreds of genes. The efficacy of many novel anticancer agents that target signal transduction pathways may be due in part to their indirect inhibition of HIF-1. Several novel compounds with anticancer activity have been shown to inhibit HIF-1 and may be useful as components of individualised multidrug therapeutic regimens chosen based on molecular analyses of tumour biopsies.