The Research Progress and Mechanism of Action of Gefitinib and Osimertinib in Non-small Cell Lung Cancer

Gefitinib is a first-generation tyrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR). It works by competitively blocking adenosine triphosphate (ATP) from binding to the kinase domain of active EGFR mutants—most often exon 19 deletions and the L858R point mutation. This blockage ultimately shrinks tumors significantly and extends progression-free survival (PFS) in patients with EGFR-mutant cancer. In contrast, osimertinib is a third-generation, irreversible EGFR TKI. It is designed to form a strong bond with the cysteine-797 (Cys-797) residue in EGFR's ATP-binding pocket. Its unique structure lets osimertinib powerfully inhibit both "sensitizing" EGFR mutations (like exon 19 deletions and L858R) and the T790M mutation—which is a common cause of resistance to first-generation EGFR TKIs. Also, osimertinib is more selective for mutant EGFR than for wild - type EGFR (wtEGFR). This indicates that it has a safer profile, particularly with fewer and less severe skin and gastrointestinal side effects, which are common problems associated with first - generation EGFR TKIs. This review consolidates key research progress, different working mechanisms, clinical effectiveness, and new resistance patterns of gefitinib and osimertinib. It specifically focuses on how they are utilized to treat EGFR - mutant non - small cell lung cancer (NSCLC).