Five other signaling pathways, including Apoptosis (Wong, 2011), Wnt (Zhan et al., 2016), Hedgehog (Gupta et al., 2010), PI3K-Akt (Brastianos et al., 2015), and TGF-beta (Massagué, 2008), show reduction in metastatic samples and in each case, their loss or dysregulation has been reported to promote the tumor growth and brain metastasis. This evidence concerns the gene AKT1 and neoplasm.