Upregulation of Ang-2 and VEGF has been demonstrated to significantly contribute to tumor growth16,46 and metastases formation.5,13 In preclinical studies dual inhibition led to improved outcomes in different tumor entities.16,17,47–50 However, the effect of early dual inhibition of Ang-2 and VEGF on BM development in mice suffering from melanoma and breast cancer using the Ang-2 inhibitor AMG 386 and the VEGF-trap aflibercept has not been investigated yet. Here, VEGFA is linked to melanoma.