HIF-1-Regulated Glucose Metabolism: A Key to Apoptosis Resistance?

Abstract

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 responsiblefor primary or acquired resistance of cancers. Hypoxia is a characteristic feature of most solidtumors and has been associated with poor treatment response. In response to hypoxia cancercells undergo a variety of adoptive changes including activation of signaling pathways, whichpromote cancer cell survival and block cell death. Hypoxia inducible factor-1 (HIF-1) is themajor transcription factor that mediates adaptation of cancer cells to the hypoxic environment.There is mounting evidence that Hif-1α, the oxygen sensitive subunit of HIF-1, providesprotection against cell death and stimulates tumor growth by upregulating genes that areinvolved in cellular energy metabolism. Thus, Hif-1α and hypoxia-inducible genes representattractive targets for the development of pharmacological inhibitors, which may offer newtherapeutic options for a wide range of adult and also pediatric malignancies.