An Overview of Osimertinib for Egfr-Mutated NSCLC With Insights Into Molecular Mechanisms and Resistance

Lung cancer is the leading cause of cancer-related deaths worldwide. The high incidence, morbidity, and mortality associated with lung cancer have driven the development of novel targeted therapies. Osimertinib (AZD9291), a novel EGFR-TKI developed by AstraZeneca, was approved by the U.S. Food and Drug Administration (FDA) in November 2015. As a tyrosine kinase inhibitor (TKI), osimertinib inhibits EGFR signaling and is an effective treatment for EGFR-mutated non-small cell lung cancer (NSCLC). The drug is specific in its mechanism of action as it targets the cysteine residue at position 797 (Cys797) near the ATP-binding pocket of the EGFR tyrosine kinase domain. A comprehensive understanding of its molecular mechanisms underlying osimertinib activity and resistance is essential for optimizing its clinical efficacy. This review provides an in-depth overview of osimertinib for clinicians, pharmacists, and researchers.