The Role of the T790M Mutation in Lung Cancer: A Molecular Perspective Based on Genetic Data

Aim: Lung cancer is one of the most common types of cancer, with non-small cell lung cancer (NSCLC) being the most prevalent subtype, accounting for approximately 85% of all cases.Tyrosine kinase inhibitors (TKIs) improve progression-free survival in patients with NSCLC and activating epidermal growth factor receptor (EGFR) mutations.However, the development of resistance has increasingly reduced the long-term efficacy of these treatments.Third-generation TKIs are designed to target drug resistance mutations, such as the T790M mutation, and have been approved as first-line treatment for advanced-stage EGFR-mutant NSCLC.In advanced-stage patients, obtaining tissue samples can be challenging.Thus, liquid biopsy for T790M mutation detection is a suitable alternative.Due to its high sensitivity, droplet digital PCR (ddPCR) is a prominent method for the detection of this protein.This study aimed to share our experience with T790M mutation analysis using ddPCR with liquid biopsy and emphasize the significance of this mutation.Methods: This study analyzed liquid biopsy data from 183 patients diagnosed with NSCLC and referred from various centers with suspected progression under first-or second-generation EGFR-TKI treatment.Using approximately 10 mL of blood samples, cell-free tumor DNA was extracted from plasma and evaluated for EGFR T790M mutation using ddPCR.Results: The T790M mutation was detected in 29 patients, including 14 male patients (15.2%) out of 92 and 15 female patients (16.48%) out of 91.In addition, other accompanying EGFR mutations were observed in 85 patients (46.45%).Among these patients, 17 (9 male and 8 female) were also found to harbor the T790M mutation. Conclusion:The ddPCR method using liquid biopsy has high sensitivity and accuracy for the molecular diagnosis of EGFR T790M mutations.Based on these combined data, this study demonstrated that ddPCR is a robust alternative method for detecting EGFR T790M mutations in plasma samples from patients with NSCLC.