PREX2 AS A MODULATOR OF THE PI3K/AKT PATHWAY IN PROSTATE CANCER PROGRESSION

Prostate cancer is one of the common cancers among men worldwide, with an estimated 1.47 million new cases reported in 2022. The PI3K/AKT signalling pathway, a key controller of cellular growth and survival, is often imbalanced in prostate tumors, essentially due to loss or mutation of PTEN, a tumor suppressor that negatively regulates this pathway. Recent research highlights the importance of PREX2, a guanine nucleotide exchange factor that activates Rac1 and directly inhibits PTEN, thereby amplifying PI3K/AKT signalling. PREX2 also modulates IRS1 stability and facilitates cytoskeletal remodelling, contributing to cancer cell migration and invasion. This review explores the structural and functional features of PREX2, its molecular interactions with PTEN, Rac1, and IRS1, its emerging role in prostate cancer progression and therapy resistance. We also discuss current limitations, recent experimental advances, and potential therapeuticstrategies targeting PREX2 and its downstream pathways.