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NGS-Based ctDNA Profiling After the Resistance of Second-Line Osimertinib for Patient with EGFR-Mutated Pulmonary
Dan Li1, DaFu Yang1, SaiQiong Cui1
1The Second Department of Thoracic Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
Abstract:
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is effective in EGFR T790M positive non-small-cell lung cancer (NSCLC). Despite the efficacy of osimertinib, patients inevitably develop resistance and the mechanisms of osimertinib resistance are heterogeneous. Here, we report that a lung adenocarcinoma patient with EGFR L858R mutation who was treated with second-line osimertinib therapy acquired multiple resistance to osimertinib by the non-invasive circulating tumor DNA (ctDNA) genotyping. This case provides the possible mechanisms of osimertinib resistance that occur during the disease progression and supports the longitudinal monitoring of ctDNA for the detection of novel acquired resistance and tumor heterogeneity.
Insights
Osimertinib effectively treats EGFR T790M positive non-small-cell lung cancer. However, acquired resistance mechanisms in lung adenocarcinoma patients treated with osimertinib can be detected using circulating tumor DNA (ctDNA) genotyping.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) used for EGFR T790M positive non-small-cell lung cancer (NSCLC).
- Acquired resistance to osimertinib is a significant clinical challenge, with heterogeneous underlying mechanisms.
- Understanding these resistance mechanisms is crucial for improving patient outcomes.
Observation:
- A case of lung adenocarcinoma with an EGFR L858R mutation is presented.
- The patient received second-line osimertinib therapy.
- Multiple osimertinib resistance mechanisms were identified through non-invasive circulating tumor DNA (ctDNA) genotyping.
Findings:
- Longitudinal ctDNA genotyping revealed acquired resistance mechanisms during osimertinib treatment.
- Tumor heterogeneity was observed in the development of osimertinib resistance.
- The study highlights the dynamic nature of resistance in EGFR-mutated NSCLC.
Implications:
- This case illustrates potential mechanisms of osimertinib resistance during disease progression.
- Longitudinal monitoring of ctDNA can detect novel acquired resistance and tumor heterogeneity.
- Non-invasive ctDNA genotyping offers a valuable tool for guiding treatment strategies in NSCLC.
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