Targeting Hypoxia-Inducible Factors for Antiangiogenic Cancer Therapy.

Hypoxia (low O ₂ ) is a pathobiological hallmark of solid cancers, resulting from the imbalance between cellular O ₂ consumption and availability. Hypoxic cancer cells (CCs) stimulate blood vessel sprouting (angiogenesis), aimed at restoring O ₂ 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.
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