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Updated: Jan 19, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Effective targeted therapy based on dynamic monitoring of gene mutations in non-small cell lung cancer
Tan Deng1, Jiao Tang1, Lijun Zhou1
1Oncology Department, Hunan Provincial People's Hospital, Changsha 410005, China.
Abstract:
With the rapid development of precision medicine, next generation sequencing (NGS) has provided the ability to decode tumors at the DNA level. In treatment of patients with non-small cell lung cancer (NSCLC), it is of great importance to identify epidermal growth factor receptor (EGFR) mutations and drug resistance mechanisms in the late stages. A Chinese Han male patient (64 years old) who was initially diagnosed with EGFR-19-deletion-positive advanced NSCLC had a satisfactory clinical response after treatment with erlotinib. Subsequently, the disease progressed and NGS in plasma-derived circulating tumor DNA (ctDNA) revealed T790M mutation. The patient was then treated with osimertinib. In addition, NGS in ctDNA was performed again after the disease progressed, suggesting that MET was amplified, and then the patient was alternatively treated with combination therapy of crizotinib and erlotinib. The disease progressed for the third time, and treatment with osimertinib was undertaken again according to the T790M testing results. Dynamic monitoring of ctDNA was found to be helpful in selecting the appropriate treatment methods and prolonging the survival time of the patient.
Insights
This case study highlights how monitoring circulating tumor DNA (ctDNA) using next-generation sequencing (NGS) guided treatment adjustments in a non-small cell lung cancer (NSCLC) patient. Dynamic ctDNA analysis identified resistance mutations, enabling personalized therapy selection and improved survival outcomes.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Precision medicine increasingly relies on next-generation sequencing (NGS) to analyze tumor DNA.
- Identifying epidermal growth factor receptor (EGFR) mutations and resistance mechanisms is crucial for advanced non-small cell lung cancer (NSCLC) treatment.
Observation:
- A 64-year-old male patient with EGFR-19-deletion-positive advanced NSCLC initially responded to erlotinib.
- Disease progression led to the identification of T790M mutation via ctDNA NGS, prompting osimertinib treatment.
- Further progression revealed MET amplification in ctDNA, leading to combination therapy with crizotinib and erlotinib.
Findings:
- Serial NGS of circulating tumor DNA (ctDNA) effectively tracked evolving resistance mechanisms in NSCLC.
- The patient received multiple lines of therapy, including erlotinib, osimertinib, and combination treatments, based on dynamic molecular profiling.
- Re-treatment with osimertinib was initiated following T790M mutation detection after disease progression.
Implications:
- Dynamic ctDNA monitoring is crucial for adapting NSCLC treatment strategies in response to acquired resistance.
- Personalized therapeutic decisions based on serial molecular profiling can potentially prolong patient survival.
- This case highlights the clinical utility of ctDNA analysis in managing advanced NSCLC with evolving resistance profiles.
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