Comprehensive Advances in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Precision Therapy

Abstract

Accounting for the highest cancer-related death burden worldwide, NSCLC, presents a significant public health challenge due to its high incidence and persistently low survival rates. Despite progress in low-dose spiral CT screening and smoking cessation campaigns, the five-year survival rate for patients diagnosed at advanced stages remains below 20%, underscoring the urgent need for optimized treatment strategies. This article synthesizes recent research advances concerning pathogenic mechanisms, diagnostic classification, and therapeutic innovations. It begins by dissecting the interaction networks between driver gene mutations and the tumor immune microenvironment, elucidating the critical role of epigenetic dysregulation in tumor progression. It subsequently reviews how the integration of liquid biopsy with artificial intelligence (AI)-enhanced imaging techniques is refining molecular subtyping. The article then provides a systematic evaluation of breakthrough clinical developments, including the iterative evolution of targeted agents (such as fourth-generation EGFR inhibitors), the expansion of immunotherapy across all treatment lines (from neoadjuvant settings to advanced disease), and the emergence of antibody-drug conjugates (ADCs) targeting HER3 and TROP2. These transformative approaches have propelled the median survival of advanced patients beyond 30 months and increased the pathological complete response rate in early-stage patients by tenfold. Studies demonstrate that biomarker-directed precision therapy is profoundly reshaping clinical practice. Future efforts must prioritize unraveling complex resistance mechanisms to further extend therapeutic benefits to all patient populations through multi-omics-guided personalized combination strategies.