Hypoxia-directed cancer therapy

Abstract

Tumour hypoxia is the result of an imbalance between oxygen supply and demand, which impacts tumour progression and treatment. Strategies of targeting hypoxic cancer cells have been under development for several decades and with the recent understanding of the biological changes under hypoxic conditions, new cancer treatments are being created. Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator composed of an O₂ ^- and growth factor-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit, which controls the expression of genes whose products are involved in tumour progression. The HIF-1α levels and HIF-1 transcriptional activity are increased by hypoxia, as well as by the signalling pathway from receptor tyrosine kinases via phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and its effector FKBP-rapamycin-associated protein (FRAP) and others. Disruption of the HIF-1 pathway inhibits tumour growth. Hypoxic cancer cells or HIF-1 may therefore be a potential anticancer target.

• gene therapy
• HIF-1
• hypoxia-directed therapy
• neoplasm