PTEN was discovered in 1997 as a tumor suppressor,364 and it was the first phosphatase proven to have tumor suppressive effects.365,366 As a phosphoinositide 3-phosphatase, PTEN negatively regulates the PI3K-AKT-mTOR pathway by converting PIP3 to PIP2, thereby hindering the proliferation and survival of tumor cells.365,367 Furthermore, PTEN exerts both enzymatic and nonenzymatic effects in cellular epithelial-mesenchymal transition (EMT), migration and invasion, glucose and lipid metabolism, cell cycle, DNA repair, genomic stability, and gene transcription.365,368. This evidence concerns the gene PIK3CA and neoplasm.