The present invention is related to the treatment of certain cancers using antagonists of the binding between a Plexin and a Sema3E. The invention may be helpful in treating primary cancer cell development and metastasis development wherein Sema3E is expressed, in particular overexpressed by the tumoral cells or the stroma. Breast cancer, in particular with distant metastases is concerned. Prostate cancer, melanoma and glioblastoma are also concerned. The antagonist may be any molecule that specifically binds to PlexinD1 or Sema3E and blocks the Sema3E/PlexinD1 binding. In an embodiment, the antagonist is a polypeptide or an antibody.