Researchers reported therapeutic approaches aimed at reversing multidrug resistance (MDR) in lung cancer, including novel small molecules, combination regimens, and delivery systems that restore chemosensitivity. Preclinical models showed re‑sensitization of resistant cell lines through inhibition of efflux pumps, modulation of survival pathways, or nanoparticle‑based drug re‑distribution. The paper outlines translational leads ready for IND‑enabling studies and suggests combination strategies with existing targeted agents or immunotherapies. Drug developers will examine pharmacokinetics, resistance biomarker panels, and potential additive toxicities as these approaches move toward clinical evaluation.