Targeting Hypoxia-Inducible Factors for Antiangiogenic Cancer Therapy

Hypoxia (low O₂) is a pathobiological hallmark of solid cancers, resulting from the imbalance between cellular O₂ consumption and availability. Hypoxic cancer cells (CCs) stimulate blood vessel sprouting (angiogenesis), aimed at restoring O₂ delivery to the expanding tumor masses through the activation of a transcriptional program mediated by hypoxia-inducible factors (HIFs). Here, we review recent data suggesting that the efficacy of antiangiogenic (AA) therapies is limited in some circumstances by HIF-dependent compensatory responses to increased intratumoral hypoxia. In lieu of this evidence, we discuss the potential of targeting HIFs as a strategy to overcome these instances of AA therapy resistance.