HIF-1-regulated glucose metabolism: a key to apoptosis resistance?

Resistance of human cancers to current treatment regimens remains a challenge in oncology. Therefore, there has been much interest in identifying molecular pathways that are responsible for primary or acquired resistance of cancers. Hypoxia is a characteristic feature of most solid tumors and has been associated with poor treatment response. In response to hypoxia cancer cells undergo a variety of adoptive changes including activation of signaling pathways, which promote cancer cell survival and block cell death. Hypoxia inducible factor-1 (HIF-1) is the major transcription factor that mediates adaptation of cancer cells to the hypoxic environment. There is mounting evidence that Hif-1alpha, the oxygen sensitive subunit of HIF-1, provides protection against cell death and stimulates tumor growth by upregulating genes that are involved in cellular energy metabolism. Thus, Hif-1alpha and hypoxia-inducible genes represent attractive targets for the development of pharmacological inhibitors, which may offer new therapeutic options for a wide range of adult and also pediatric malignancies.