We provide a significant discussion on SPDEF (SAM Pointed Domain Containing ETS Transcription Factor), ERG, androgen receptor (AR), Activating Protein-1 (AP-1), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and MYC in PCa development, focusing on the molecular mechanisms involved in PCa development as well as their use in diagnostics and therapeutic approaches. This evidence concerns the gene ERG and posterior cortical atrophy.