However, questions remain: potential predictive markers for these VEGF-A/VEGFR-2 pathway inhibitors, whether colorectal cancer may develop crossover tolerability/resistance to these treat different agents, potential opportunities to the possible mechanisms of moderate benefits (~1.4 months survival advantage) of these anti-angiogenic agents in mCRC, and possibilities of these anti-angiogenic agents in combination with other biologic target oriented agents, in particular immune checkpoint inhibitors. This evidence concerns the gene VEGFA and colorectal cancer.