Hypoxia — a key regulatory factor in tumour growth

Abstract

Hypoxia is a reduction in the normal level of tissue oxygen tension, and occurs during acute and chronic vascular disease, pulmonary disease and cancer. It induces a transcription programme that promotes an aggressive tumour phenotype. Hypoxia is associated with resistance to radiation therapy and chemotherapy, but is also associated with poor outcome regardless of treatment modality, indicating that it might be an important therapeutic target. Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor that is induced by hypoxia and regulated by a proline hydroxylase. Pathways that are regulated by hypoxia include angiogenesis, glycolysis, growth-factor signalling, immortalization, genetic instability, tissue invasion and metastasis, apoptosis and pH regulation. Most of the hypoxia-induced pathways promote tumour growth, but apoptosis is also induced by hypoxia. The balance of these pathways might be critical for the effects of hypoxia on tumour growth. Drugs that inhibit HIF-1α expression antagonize HIF-1α interaction with CBP/p300 or block downstream function of genes such as vascular endothelial growth factor and cyclooxygenase-2 have potentially important roles in tumour therapy. Hypoxia can also be used to activate therapeutic gene delivery to specific areas of tissue.