Advancements in mTOR Inhibitors for Non-Small-Cell Lung Cancer: Mechanisms, Efficacy, and Future Perspectives

Abstract This account comprehensively reviews the recent advancements in the development of mechanistic target of rapamycin (mTOR) inhibitors targeting non-small-cell lung cancer (NSCLC), focusing on their mechanisms, efficacy, and clinical trial statuses. Key small molecules such as RM-018 and RMC-4998 highlight novel approaches in targeting the KRASG12C mutation, offering enhanced potency compared to earlier inhibitors. Traditional and plant-derived compounds, including Fuzi alkaloids, salvianolic acid, and ononin, demonstrate promising antitumor activities through diverse pathways, such as the PI3K/AKT/mTOR signaling axis. Combination therapies targeting dual pathways show synergistic effects, improving treatment efficacy. The role of personalized medicine, driven by genetic profiling and pathway-specific inhibitors, is emphasized as a transformative approach in NSCLC management. These findings highlight the potential of mTOR-targeting agents as a cornerstone in advancing NSCLC therapies. 1 Introduction 2 Small-Molecule mTOR Inhibitors 3 mTOR Inhibitors in Clinical Trials 4 Conclusion and Future Directions