Using cell models mimicking early and advanced PCa, we demonstrate that ERG and ETV1 differentially regulate the activation of EGFR, STAT3, and STAT5A in prostate cells, which modulates sensitivity to Erlotinib (EGFR inhibitor) and TTI‐101 (STAT3 inhibitor) synergistic inhibition in both 2D and 3D PCa cell models. This evidence concerns the gene STAT3 and posterior cortical atrophy.