ADDRESSING CHEMORESISTANCE IN LUNG CANCER: PATHWAYS AND THERAPEUTIC APPROACHES

One of the primary obstacles to treating lung cancer is chemoresistance, which substantially impacts patient survival and quality of life. This review delves into the complex biological mechanisms underlying chemoresistance, including cellular adaptations such as drug efflux, enhanced DNA repair, metabolic alterations, and evasion of apoptosis. The importance of the tumor microenvironment (TME) is crucial, with hypoxia, stromal interactions, and immune evasion fostering resistance. Additionally, tumor heterogeneity is influenced by epigenetic changes, cancer stem cells (CSCs), and resistance persistence. To address these challenges, innovative therapeutic strategies have been developed. Approaches that target drug efflux pumps, modulate the TME, and employ epigenetic therapies show promise in overcoming resistance. Nanotechnology-based drug delivery systems are emerging as effective means to enhance drug targeting while minimizing systemic toxicity. Furthermore, combination therapies integrating chemotherapy with targeted agents or immunotherapy are gaining traction, offering synergistic effects to combat resistance. This review highlights recent advancements in preclinical and clinical research, emphasizing the need for personalized treatment strategies and biomarker-driven approaches to predict and overcome resistance. Future directions call for the integration of novel technologies such as single-cell sequencing and AI-driven drug discovery to elucidate the dynamic nature of resistance mechanisms and improve therapeutic outcomes. By advancing our understanding of chemoresistance biology and therapeutic interventions, this review aims to inspire innovative solutions to one of the most urgent issues in the treatment of lung cancer.