Pharmacological strategies to overcome immune checkpoint inhibitor resistance in non-small cell lung cancer
Pharmacological strategies can overcome immune checkpoint inhibitor resistance in NSCLC
Immune checkpoint inhibitors (ICIs) have redefined the therapeutic paradigm of non-small cell lung cancer (NSCLC), offering durable remission in select patients by reactivating anti-tumor T cell responses. Yet, this clinical triumph is tempered by the reality that most patients experience either primary resistance or relapse due to acquired resistance, underscoring an urgent need for mechanistically grounded solutions. Resistance arises through a complex interplay of tumor‑intrinsic mechanisms, including defects in antigen presentation, interferon signaling disruption, and oncogenic pathway activation (EGFR, KRAS, MET), and tumor‑extrinsic factors such as immunosuppressive cell populations, inhibitory cytokines, and metabolic rewiring of the tumor microenvironment (TME). This review provides a comprehensive synthesis of emerging pharmacological strategies aimed at reversing ICI resistance in NSCLC. Promising avenues include dual or multi‑checkpoint inhibition (targeting LAG‑3, TIGIT, TIM‑3), integration of epigenetic reprogrammers to resensitize immune‑silent tumors, and metabolic interventions that normaliz
Evidence level: Feltételezés / hírjelzés. Nincs önálló tudományos bizonyíték.
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