Resistance mechanisms of non-small cell lung cancer and improvement of treatment effects through nanotechnology: a narrative review.

Background and objective: Lung cancer continues to be the leading cause of cancer-related deaths globally. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Although targeted therapies and immune checkpoint inhibitors have improved clinical outcomes for NSCLC patients, primary and acquired resistance remain significant obstacles to effective treatment. This review aims to elucidate the molecular mechanisms of NSCLC resistance and explore the potential of nanotechnology-based drug delivery systems in overcoming these resistance barriers.

Methods: The research team conducted a comprehensive literature search in PubMed, Cochrane Library, Google Scholar, Embase, Web of Science, China National Knowledge Internet (CNKI), and Wanfang Database, covering the period from January 1st, 2007 to January 1st, 2024.

Key content and findings: This review summarizes the molecular mechanisms of NSCLC resistance, including target alterations, bypass signaling pathways, phenotypic transformations, and immunosuppressive mechanisms. It discusses the use of nanotechnology-based drug delivery systems (such as polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles) to overcome various resistance barriers. Additionally, it highlights the role of nanotechnology-based immunotherapeutic strategies in modulating tumor immunity. The review also explores methods for rationally designing combination nanomedicine strategies to address resistance issues at multiple levels, thereby enhancing the effectiveness of NSCLC treatment.

Conclusions: A deep understanding of the mechanisms of NSCLC resistance and the innovative application of nanotechnology-based delivery strategies are crucial for improving patient survival. Rationally designing combination nanomedicine strategies that target multiple resistance mechanisms simultaneously holds promise for overcoming NSCLC resistance and enhancing treatment effectiveness. Further research is needed to investigate the clinical translation of emerging nanotechnologies, providing more effective treatment strategies for NSCLC patients.