EGFR T790M mutation detection in NSCLC patients resistant to tyrosine kinase inhibitor therapy
Kadyrbayeva R. Kaidarova D. Shatkovskaya O. Goncharova T. Orazgalieva M. Ossikbayeva S.
December 2024Edizioni Minerva Medica
Panminerva Medica
2024#66Issue 4372 - 379 pp.
BACKGROUND: The finding of mutations that activate epidermal growth factor receptor (EGFR) in people with lung adenocarcinoma resulted in the creation of a new class of biological treatments called tyrosine kinase inhibitors (TKI). These medications have changed how patients with EGFR mutations are clinically managed, nearly doubling their survival rate compared to standard chemotherapy. Though 1st and 2nd generation EGFR TKIs are initially highly effective, typically within 9-14 months all tumors with the mutation progress due to secondary resistance mutations involving alternative molecular pathways. In most cases (up to 60%), this is due to the T790M mutation emerging in the EGFR gene. METHODS: The study included 85 patients with NSCLC with progression of the disease after treatment with TKI 1st and 2nd generation. The T790M mutation was determined by digital polymerase chain reaction (PCR) on the QIAcuity One 5plex digital PCR system and traditional real-time PCR. Real-time PCR analysis of the presence of the T790M mutation was performed using the Therascreen EGFR Plasma RGQ PCR Kit (Qiagen). Using a digital PCR system in QIAcuity One (Qiagen) nanoplanets, the T790M mutation was analysed by digital PCR. The age of the patients ranged from 37 to 85 years. RESULTS: Of 85 patients with NSCLC with disease progression after TKI treatment, T790M mutations were detected during digital PCR in 30 of 85 patients, which is 35.2% of the sample, and with traditional real-time PCR, positive mutations came out only in 3 out of 85 patients. CONCLUSIONS: Thus, completed study can assert that digital PCR is able to replace traditional real-time PCR as a more preferable method of high-performance quantitative determination of target nucleic acids and has a relatively high sensitivity without compromising high specificity. Results of this research also show that a liquid biopsy using digital PCR provides an opportunity to avoid repeated tissue biopsy in patients who cannot provide a tumor tissue sample suitable for molecular analysis.
Liquid biopsy , Lung neoplasms , Molecular targeted therapy , Non-small-cell lung cancer
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Chemotherapy Center, Kazakh Institute of Oncology and Radiology, Almaty, Kazakhstan
Department of Oncology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
Kazakh Institute of Oncology and Radiology, Almaty, Kazakhstan
Center for Molecular Genetic Research, Kazakh Institute of Oncology and Radiology, Almaty, Kazakhstan
Chemotherapy Center
Department of Oncology
Kazakh Institute of Oncology and Radiology
Center for Molecular Genetic Research
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