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Salvage Surgery for Advanced Lung Adenocarcinoma After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
Mong-Wei Lin1, Sung-Liang Yu2, Yin-Chen Hsu3
1Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Background:
No published studies to date have evaluated the detailed pathologic and genetic features of lung adenocarcinoma after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and salvage surgery. We aimed to evaluate the pathologic and genetic changes of tumors in patients with advanced lung adenocarcinoma treated with EGFR TKI therapy and salvage surgery.
Methods:
This study retrospectively collected data from 29 advanced lung adenocarcinoma patients who underwent EGFR TKI therapy, followed by salvage operation, between January 2010 and December 2018. All patients had partial response or stable disease without evidence of progressive disease. Next-generation sequencing was used to determine whether acquired resistant mutations in morphologically treatment-sensitive and morphologically treatment-resistant regions of tumor existed.
Results:
There were 3, 22, and 4 patients with clinical stage IIIB, IVA, and IVB, respectively. After a mean TKI treatment duration of 134 days, 27 patients had partial response, 2 had stable disease, and 27.6% of patients were downstaged before salvage surgery. All patients had residual viable tumor cells in their tumor bed; 5 patients (17.2%) had a major pathologic response. Acquired T790M mutations (n = 4), histologic transformations (n = 2), and acquired T790M mutation with histologic transformation (n = 1) were identified in the morphologically treatment-resistant regions of tumors. The 3-year overall survival was 75.9%.
Conclusions:
The presence of morphologically treatment-resistant tumor regions with acquired T790M mutations and histologic transformations demonstrate the existence of resistant subclones in TKI-treated tumors before disease progression. Salvage surgery performed in selected patients before disease progression may improve survival by removing TKI-resistant subclones.
Insights
This study reveals that lung adenocarcinoma tumors can develop resistance mutations and transformations even before disease progression after EGFR TKI therapy. Salvage surgery may improve survival by removing these resistant subclones.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Limited data exists on the detailed pathologic and genetic changes in lung adenocarcinoma following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and salvage surgery.
- This study addresses this gap by examining tumors from patients treated with EGFR TKI therapy and subsequent salvage surgery.
Purpose of the Study:
- To evaluate the pathologic and genetic alterations in advanced lung adenocarcinoma tumors after EGFR TKI treatment and salvage surgery.
- To identify acquired resistance mechanisms and their impact on patient outcomes.
Main Methods:
- Retrospective analysis of 29 advanced lung adenocarcinoma patients treated between 2010 and 2018.
- Utilized next-generation sequencing to detect acquired mutations in treatment-sensitive and resistant tumor regions.
- Assessed pathologic responses and histologic transformations post-TKI therapy.
Main Results:
- A significant proportion of patients (27.6%) were downstaged before salvage surgery.
- Residual viable tumor cells were present in all patients; 17.2% showed a major pathologic response.
- Acquired T790M mutations and histologic transformations were identified in resistant tumor regions, indicating pre-progression resistance.
- The 3-year overall survival rate was 75.9%.
Conclusions:
- Morphologically resistant tumor regions with acquired T790M mutations and histologic transformations signify the presence of resistant subclones before disease progression.
- Salvage surgery in selected patients prior to disease progression may enhance survival by excising these TKI-resistant subclones.
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