Biomarkers of angiogenesis and their role in clinical oncology
Tumour angiogenesis has been identified to play a critical role in tumour growth and tumour progression. Multiple angiogenic factors are involved in the regulation of angiogenesis. Amongst them VEGF (vascular endothelial growth factor) and its receptors (VEGFRs) are of crucial relevance. Inhibition of VEGF/R signalling by monoclonal antibodies or small molecules as receptor tyrosinekinase inhibitors has already been successfully established for the treatment of various cancer entities. Bevacizumab, a monoclonal antibody against VEGF, as well as sorafenib and sunitinib, both small molecules, are already approved for clinical practice. Furthermore, an ever-expanding list of new anti-angiogenic agents is under advanced clinical development, some of which are already being considered for approval. However, not all patients treated with anti-angiogenic therapies benefit from this kind of therapy and in most cases, the effect is transient. Therefore, there is an urgent need for biomarkers to identify patients likely to benefit from anti-angiogenic treatments, to select the optimal dose and to understand the mechanisms of resistance. Preclinical models suggest multiple mechanisms involved in acquired or primary resistance against anti-angiogenic therapies, but only few data are available from clinical studies evaluating surrogate markers during therapy. The present review summarizes the different types of biomarkers for anti-angiogenic therapies and gives an overview of resistance mechanisms to anti-angiogenic therapies.