This study investigates the detection of EGFR mutations in circulating tumor cells (CTCs) from patients with non-small-cell lung cancer (NSCLC). The researchers developed a microfluidic device, the CTC-chip, to capture and analyze CTCs from blood samples. They found that the CTC-chip could isolate high-purity CTCs with sufficient quantity for molecular analysis. The study used allele-specific polymerase chain reaction (PCR) amplification to detect EGFR mutations, including the activating mutations and the T790M mutation, which confers drug resistance. The results showed that the CTC-chip successfully identified EGFR mutations in 92% of patients with metastatic NSCLC and in 33% of matched free plasma DNA samples. The presence of T790M in pretreatment tumor samples was associated with reduced progression-free survival. Serial analysis of CTCs during treatment revealed that a reduction in CTCs correlated with a radiographic tumor response, while an increase in CTCs indicated tumor progression and the emergence of additional EGFR mutations. The study concludes that molecular analysis of CTCs from blood can provide a strategy for noninvasive monitoring of tumor genotypes during treatment, offering insights into treatment response and resistance mechanisms.This study investigates the detection of EGFR mutations in circulating tumor cells (CTCs) from patients with non-small-cell lung cancer (NSCLC). The researchers developed a microfluidic device, the CTC-chip, to capture and analyze CTCs from blood samples. They found that the CTC-chip could isolate high-purity CTCs with sufficient quantity for molecular analysis. The study used allele-specific polymerase chain reaction (PCR) amplification to detect EGFR mutations, including the activating mutations and the T790M mutation, which confers drug resistance. The results showed that the CTC-chip successfully identified EGFR mutations in 92% of patients with metastatic NSCLC and in 33% of matched free plasma DNA samples. The presence of T790M in pretreatment tumor samples was associated with reduced progression-free survival. Serial analysis of CTCs during treatment revealed that a reduction in CTCs correlated with a radiographic tumor response, while an increase in CTCs indicated tumor progression and the emergence of additional EGFR mutations. The study concludes that molecular analysis of CTCs from blood can provide a strategy for noninvasive monitoring of tumor genotypes during treatment, offering insights into treatment response and resistance mechanisms.