AKT1 and urinary bladder cancer: A549 combinations did not outperform 5-FU; PC-3 was largely unresponsive.<h4>Conclusions</h4>cAMP modulators selectively potentiate 5-FU in bladder cancer cells and modulate redox programs (notably with terbutaline), supporting a biomarker-guided combination strategy (e.g., β2-AR/PDE3/PI3K-Akt features) for personalized therapy in bladder cancer; mechanistic and in vivo validation are warranted.