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. Keywords:: hypoxia-inducible factor (HIF), protein transduction domain, oxygen-dependent degradation, bioluminescence imaging, pancreatic cancer