Normoxic or hypoxic adaptation in response to antiangiogenic therapy: Clinical implications.

In a recent article in Cell Reports, we described a novel mechanism for acquired resistance against new small-molecule antiangiogenic tyrosine-kinase inhibitors (TKIs). Vascular normalization-inducing TKIs block glycolysis and trigger a nutritional stress response in the tumor compartment that induces a (targetable) switch to mitochondrial metabolism. We discuss the implications for clinical/translational studies and suggest areas for future research.