PGP and cancer: This encompasses the rational design of next-generation P-gp modulators with improved specificity (e.g., reduced interaction with physiological P-gp, minimal impact on beneficial immune cells) and favorable pharmacokinetic/pharmacodynamic profiles, alongside the exploration of innovative drug delivery systems (e.g., nanoparticles targeting cancer cells) and rational combination therapies designed to bypass or overcome efflux mechanisms based on the specific resistance profile of the tumor.