Hijacking the vasculature in ccRCC—co-option, remodelling and angiogenesis

The most common type of malignancy in the adult kidney is clear cell renal cell carcinoma (ccRCC), for which antiangiogenic therapy with surgery is currently the standard treatment. Although overall survival of patients with metastatic ccRCC has been substantially extended by antiangiogenic therapy with agents such as sorafenib and sunitinib, patients almost certainly go on to develop resistance, or present at the time of treatment with primary resistance. This eventuality implies that our knowledge of the processes involved in tumour angiogenesis in ccRCC is superficial. Increasing evidence has shown that a solid tumour can, during invasion and expansion, 'hijack' pre-existing blood vessels and integrate them into the tumour vasculature. This approach to expanding the tumour vasculature is referred to as vessel co-option. In this Perspectives article, I argue that vessel co-option likely occurs in ccRCC, along with the complementary processes of vessel remodelling and extratumoural angiogenesis. Exploring the underlying molecular mechanisms of these complicated vasculature developments in ccRCC might provide new opportunities to enhance the efficacy of antiangiogenic therapy.