PTEN and Familial prostate cancer: It is conceivable that in PTEN-null prostate cancers with lower levels of PIM expression, such as in early stage CRPC or hormone sensitive disease represented by the LNCaP cells, PIM upregulation can occur as an acquired or adaptive resistance after initial sensitivity to AKT inhibition, while in more advanced tumors where further increase in PIM expression occurs, intrinsic resistance to AKT inhibitors may be observed.