fig1

Figure 1. Mechanisms of osimertinib resistance. Note: Resistance mechanisms are classified by current therapeutic actionability. Clinically targetable: MET amplification (savolitinib, tepotinib, and amivantamab), HER2 amplification (trastuzumab deruxtecan), and ALK/RET/ROS1/NTRK fusions (corresponding selective TKIs). Under clinical investigation: C797S mutation (fourth-generation allosteric EGFR inhibitors, e.g., BLU-945), PIK3CA/PTEN alterations (AKT inhibitors), and RAS/MAPK activation (MEK inhibitor combinations). No established targeted strategy exists for SCLC: histological transformation (managed with platinum-etoposide chemotherapy), squamous transformation, or polyclonal multipathway resistance.