Replication stress response and radioresistance in lung cancer: Mechanistic insights and advanced therapeutic approaches

Abstract

Lung cancer, the leading cause of cancer mortality globally, comprises mainly non-small cell lung cancer and small cell lung cancer. Its pathogenesis involves genetic mutations, environmental exposures, chronic inflammation, and tumor microenvironment interactions. Critical genes like TP53, RB1, KRAS, and EGFR often mutate, driving uncontrolled cell growth. Radiation therapy, a primary treatment, faces challenges with radioresistance due to DNA repair mechanisms and replication stress responses. Emerging therapeutic strategies target DNA repair pathways, cell cycle checkpoints, and immune responses to enhance radiosensitivity and counteract resistance. Promising approaches include PARP inhibitors, CDK inhibitors, EGFR blockers, and immunotherapies combined with radiation. Advances in understanding these mechanisms are crucial for developing targeted therapies to improve lung cancer patient outcomes. The present review focuses on elucidating the intricate mechanisms of lung cancer pathogenesis and radioresistance, while highlighting novel therapeutic strategies designed to overcome these challenges and improve treatment efficacy.