While advances in artificial intelligence-based algorithms, digital spatial profiling, and the generation of new clinically relevant models of prostate cancer that span a range of different disease subtypes are beginning to address these points, the continued exploration into PTEN function, PI3K--AKT--mTOR inhibition and prostate cancer biology is essential for the identification of new therapeutic approaches and valuable predictive biomarkers that will help to refine future personalized therapies for PTEN-deficient prostate~cancer. This evidence concerns the gene PIK3CA and Familial prostate cancer.