Antiangiogenic therapy, hypoxia, and metastasis: risky liaisons, or not?

All human cells, including cancer cells, need oxygen and nutrients to survive. A widely used strategy to combat cancer is therefore the starvation of tumor cells by cutting off the blood supply of tumors. Clinical experience indeed shows that tumor progression can be delayed by anti-angiogenic agents. However, emerging evidence indicates that in certain experimental conditions, hypoxia as a result of pruning of the tumor microvasculature can promote tumor invasion and metastasis, although these findings are contextual and debated. Genetic studies in mice unveiled that vascular-targeting strategies that avoid aggravation of tumor hypoxia or even promote tumor oxygenation might prevent such an invasive metastatic switch. In this article, we will discuss the emerging link between hypoxia signaling and the various steps of metastasis.