Targeting Angiogenesis in Colorectal Carcinoma

Neo-angiogenesis plays a key role in colorectal cancer, with the vascular endothelial growth factor family proteins and their receptors in particular triggering multiple signaling networks that result in endothelial cell survival, migration, mitogenesis, differentiation, and vascular permeability. Anti-angiogenic therapies have improved colorectal cancer prognosis within the past 15 years. Bevacizumab demonstrated efficacy in combination with chemotherapy under different conditions, including as first- and second-line therapies, and also as a maintenance treatment strategy. Other drugs targeting angiogenesis effectors (e.g., ramucirumab and aflibercept) were approved after bevacizumab failure, confirming the concept of “continuous anti-angiogenic blocking”. Recently, a number of new orally available multiple receptor tyrosine kinase inhibitors have been tested in late-stage clinical trials, with modest efficacy. Due to the availability of several anti-angiogenic agents, we need well-designed prospective randomized trials to optimize therapeutic sequencing. The place of biosimilars in the therapeutic armamentarium remains unclear at the moment. Further research is warranted to identify robust predictive biomarkers of efficacy and innovative clinically meaningful anti-angiogenic drugs that are cost-efficient.