Exploring the Impact of Multiple Gene Mutations on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Response in Asian Nonsmall Cell Lung Cancer Patients.

Nonsmall cell lung cancer (NSCLC) is characterized by diverse genetic alterations, among which epidermal growth factor receptor (EGFR) mutations are the most common, particularly in adenocarcinoma, occurring in 10-15% of patients. However, in Asian populations, the EGFR mutation rate can be as high as 51.4%. Other mutations such as Kirsten rat sarcoma viral oncogene (KRAS), anaplastic lymphoma kinase, rearranged during transfection, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, human EGFR 2 (HER2), V-Raf murine sarcoma viral oncogene homologue B (BRAF), mesenchymal-epithelial transition, and c-ros oncogene 1 (ROS1) are also frequently observed. EGFR mutations may co-occur with these alterations, influencing response to targeted therapy. The advent of EGFR tyrosine kinase inhibitors (TKI) (EGFR-TKIs) has markedly improved treatment outcomes in EGFR-mutant NSCLC. However, approximately 20%-30% of patients still develop primary or acquired resistance to EGFR-TKIs. Emerging evidence suggests that concurrent gene mutations contribute significantly to this resistance. Therefore, different EGFR subtypes and coexisting mutations may affect TKI efficacy. This review highlights the mutation spectrum of Asian NSCLC patients, particularly focusing on concurrent mutations and their impact on EGFR-TKI response. We also discuss evolving treatment strategies and summarize ongoing clinical trials targeting comutation scenarios. These insights may help guide personalized therapy decisions and provide directions for future research.