Targeting shared mechanisms of cisplatin resistance and metastasis in lung cancer for novel therapeutic strategies

Cisplatin, a cornerstone therapeutic agent in lung cancer chemotherapy, is significantly limited by the development of drug resistance, which remains a principal driver of treatment failure. Investigations have demonstrated that cisplatin-resistant lung cancer cells frequently acquire an enhanced metastatic phenotype, which is correlated with severely adverse clinical outcomes. Growing evidence indicates that chemoresistance and metastasis share underlying molecular pathways and exhibit mutually reinforcing relationships. Key mechanisms include metabolic reprogramming, epithelial‒mesenchymal transition (EMT), immunosuppressive microenvironment remodeling, and adaptive activation of prosurvival signaling pathways, which collectively contribute to accelerated disease progression and diminished patient survival. This review provides recent insights into the pathogenic crosstalk between cisplatin resistance and metastasis, and discusses integrated targeting strategies designed to overcome the limitations of conventional monotherapy.