Alpha-2 macroglobulin (A2M), a large plasma glycoprotein natural inhibitor of cathepsin B and many other growth factors especially epidermal growth factors, exhibits the capability of abrogating the malignant potential of astrocytoma cells such as cell proliferation, invasion, and migration, and, as such, it can be exploited for therapeutic purposes [25, 26, 42–46]. This evidence concerns the gene A2M and astrocytoma (excluding glioblastoma).