Abstract

Therapeutic resistance poses a significant challenge in the effective management of lung cancer, particularly in advanced stages. Despite advancements in targeted therapies, immunotherapies, and chemotherapy, many patients develop resistance, leading to disease progression and reduced survival rates. This review explores the underlying mechanisms driving therapeutic resistance in lung cancer, including genetic mutations, tumor heterogeneity, epithelialmesenchyme transition (EMT), and the tumor microenvironment’s immunosuppressive dynamics. Additionally, we highlight the role of cancer stem cells and adaptive signaling pathways in fostering resistance. Emerging strategies to overcome therapeutic resistance are discussed, emphasizing combination therapies, next-generation inhibitors, and novel approaches such as targeting resistance pathways, enhancing immune responses, and leveraging liquid biopsies for real-time monitoring of tumor evolution. Preclinical and clinical evidence supporting these approaches is evaluated, offering insights into their potential to improve patient outcomes. By addressing the multifaceted nature of resistance, this review underscores the importance of a precision medicine framework in designing personalized interventions and advancing the fight against lung cancer.