Assuming that an increased Ang-2 and VEGF expression may change the local perivascular microenvironment towards a supporting pre-metastatic environment at the early stages of the metastatic cascade, we further tested whether combined treatment with AMG 38626 (a peptibody binding to angiopoietin-1 and angiopoietin-2) and aflibercept27,28 (a fusion protein containing domains of VEGFR1 and VEGFR2, thereby acting as “VEGF Trap”) at early stages may inhibit melanoma and breast carcinoma BM formation. This evidence concerns the gene ANGPT2 and breast carcinoma.