English Version
Background
The use of t yrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non–small-cell lung cancer is effective but limited by the emergence of drug-resistance mutat ions. Molecular characterizat ion of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment.
Methods
We captured highly purif ied circulat ing tumor cel ls from the blood of pat ients with non smal l-cel l lung cancer using a microf luidic device containing microposts coated with antibodies against epithelial cells. We performed EGFR mutational analysis on DNA recovered from circulating tumor cells using allele-specific polymerasechain-reaction amplif ication and compared the results with those from concurrently isolated free plasma DNA and from the original tumor-biopsy specimens.
The use of t yrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non–small-cell lung cancer is effective but limited by the emergence of drug-resistance mutat ions. Molecular characterizat ion of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment.
Methods
We captured highly purif ied circulat ing tumor cel ls from the blood of pat ients with non smal l-cel l lung cancer using a microf luidic device containing microposts coated with antibodies against epithelial cells. We performed EGFR mutational analysis on DNA recovered from circulating tumor cells using allele-specific polymerasechain-reaction amplif ication and compared the results with those from concurrently isolated free plasma DNA and from the original tumor-biopsy specimens.
Results
We isolated circulat ing tumor cel ls f rom 27 pat ients with metastat ic non–smal l-cel l lung cancer (median number, 74 cells per milliliter). We identified the expected EGFR activating mutation in circulating tumor cells from 11 of 12 patients (92%) and in matched free plasma DNA from 4 of 12 patients (33%) (P = 0.009). We detected the T790M mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutat ions who had received t yrosine kinase inhibitors. When T790M was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival (7.7 months vs. 16.5 months, P<0.001). Serial analysis of circulat ing tumor cel ls showed that a reduction in the number of captured cells was associated with a radiographic tumor response; an increase in the number of cells was associated with tumor progression, with the emergence of additional EGFR mutations in some cases. Conclusions Molecular analysis of circulating tumor cells from the blood of patients with lung cancer offers the possibility of monitoring changes in epithelial tumor genotypes during the course of treatment.
Journals for full download on the link below.
We isolated circulat ing tumor cel ls f rom 27 pat ients with metastat ic non–smal l-cel l lung cancer (median number, 74 cells per milliliter). We identified the expected EGFR activating mutation in circulating tumor cells from 11 of 12 patients (92%) and in matched free plasma DNA from 4 of 12 patients (33%) (P = 0.009). We detected the T790M mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutat ions who had received t yrosine kinase inhibitors. When T790M was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival (7.7 months vs. 16.5 months, P<0.001). Serial analysis of circulat ing tumor cel ls showed that a reduction in the number of captured cells was associated with a radiographic tumor response; an increase in the number of cells was associated with tumor progression, with the emergence of additional EGFR mutations in some cases. Conclusions Molecular analysis of circulating tumor cells from the blood of patients with lung cancer offers the possibility of monitoring changes in epithelial tumor genotypes during the course of treatment.
Journals for full download on the link below.
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