In the preclinical metastatic melanoma setting, combination with immunotherapy was shown to overcome resistance to anti-VEGF treatment as exemplified by tumor regression upon anti-PD-1 treatment, which elicits humoral immune responses by inducing anti-ANGPT2 serum IgG against ANGPT-2-derived bevacizumab resistance [181]. This evidence concerns the gene ANGPT2 and metastatic melanoma.