The value of anti-angiogenics in bladder cancer therapy

Abstract

The therapy of metastatic bladder cancer (BC) mainly relies on platinum-based chemotherapy with very limited options like vinflunine in the second line. Therefore, there has not been much change in the median survival of this patient cohort within the last decades. Angiogenesis is a well-proven patho-mechanism in BC. Different angiogenic pathways have been elucidated within the last 20 years, among them vascular endothelial growth factor (VEGF), angiopoietin/Tie, matrix metalloproteinases (MMPs), fibroblast growth factor (FGF), thrombospondin 1 (TSP1), and hypoxiainducible factor (HIF) as the most prominent ones. In order to be able to understand the mechanisms of novel compounds, it is helpful to have a basic knowledge of the relevance of these signaling pathways in the field ofBC. Therefore, we not only sum up the majority of clinical studies on anti-angiogenics in BC but also explain the most important pathways responsible for bladder tumor angiogenesis in this chapter. Many established anti-angiogenics like bevacizumab, sunitinib, sorafenib, aflibercept, pazopanib, and vandetanib have been tested in clinical trials for BC. Furthermore, the pipelines are filled with clinical trials on novel anti-angiogenic drugs like ramucirumab, icrucumab, regorafenib, nintedanib, and many more. However, no compound has yet proven significant single-agent efficacy. Therefore, up to now, no anti-angiogenic drug has been approved for BC therapy. Consequently, future clinical trials will not only have to test for new anti-angiogenics, but also for different treatment algorithms as well as combination therapies. Although most of the studies showed disappointing overall results, subcohorts had a significant benefit. Therefore, novel approaches should increasingly focus on identifying patient subgroups with the greatest susceptibility to the respective anti-angiogenic therapy.