Pathophysiological response to hypoxia - From the molecular mechanisms of malady to drug discovery: Hypoxia-inducible factor-1 (HIF-1)-active cells as a target for cancer therapy

Abstract

The microenvironment of solid tumors is characterized by low pO2 that is well below physiological levels. Intratumoral hypoxia is a major factor contributing to cancer progression and is exacerbated as a result of oxygen consumption by rapidly proliferating tumor cells near blood vessels, poor lymphatic drainage resulting in high interstitial pressure, and irregular blood supply through immature tumor vasculature. Hypoxia-inducible factor-1 (HIF-1) is the main transcription factor that regulates cellular responses to hypoxia. Cellular changes induced by HIF-1 are extremely important targets for cancer therapy. Therefore, targeting strategies to counteract HIF-1-active cells are essential for cancer therapy. In this study, we introduce a novel strategy for targeting HIF-1-active cells. © The Japanese Pharmacological Society.