Biomarker-guided targeted therapy in lung adenocarcinoma: A concise review of precision oncology advances, resistance mechanisms, and emerging strategies.

Lung adenocarcinoma (LUAD), a major subtype of non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality despite major therapeutic advances. Precision oncology has revolutionized the management of LUAD by identifying actionable molecular biomarkers and developing targeted therapies. In this review, we summarize the major predictive biomarkers in LUAD, including EGFR, KRAS, ALK, ROS1, MET, RET, BRAF, HER2, NTRK, and PD-L1, and describe the currently approved targeted therapies and emerging therapeutic strategies. Recent advances in selective inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors that have improved clinical outcomes in molecularly defined patient populations are highlighted. The review also discusses the molecular basis of acquired resistance, such as on-target mutations, bypass signalling activation, histological transformation, and epithelial-mesenchymal transition that continue to limit long-term therapeutic efficacy. We also discuss emerging strategies to overcome resistance, including combination therapies, next-generation inhibitors, liquid biopsy-guided monitoring, and artificial intelligence-assisted precision medicine. Collectively, these findings highlight the need for comprehensive molecular characterization and integrated biomarker-guided treatment strategies to improve therapeutic decision-making and clinical outcomes in LUAD.