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Association Between EGFR T790M Status and Progression Patterns During Initial EGFR-TKI Treatment in Patients
Yuko Oya1, Tatsuya Yoshida1, Hiroaki Kuroda2
1Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
Background:
Emergence of the T790M point mutation in exon 20 of the epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The aim of this study was to investigate the association between T790M mutation status and the progression patterns during EGFR-TKI treatment.
Methods:
We reviewed 181 patients with advanced non-small-cell lung cancer harboring EGFR mutation, who were evaluated for T790M mutation status after initial EGFR-TKI failure (gefitinib, erlotinib, or afatinib). We retrospectively investigated the patient characteristics, initial EGFR-TKI response, T790M mutation status, subsequent treatment after initial EGFR-TKIs, timing of re-biopsy, and progression patterns during the EGFR-TKI treatment.
Results:
After the resistance to the EGFR-TKIs, the T790M mutation was identified in 87 (48%) of 181 patients. Seventy-three (40%) patients had solitary lesion progression, and 108 (60%) had multiple lesion progression during the initial EGFR-TKI treatment. The prevalence of the T790M mutation was significantly greater in patients with solitary lesion progression than those with multiple lesion progression (58% vs. 24%; P < .0001). The overall response rate and progression-free survival on initial EGFR-TKIs were significantly better in patients who acquired T790M after failure of EGFR-TKIs than those without T790M (overall response rate, 80% vs. 60%; P = .0033 and progression-free survival, 11.4 vs. 9.3 months; P = .0050). The multivariate analysis showed that gender, initial EGFR-TKI response, and progression patterns were significantly associated with T790M mutation status.
Discussion:
The progression patterns during initial EGFR-TKIs and initial EGFR-TKI response are associated with the T790M mutation.
Insights
The T790M mutation, a common resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs), is linked to specific progression patterns in non-small-cell lung cancer. Solitary lesion progression is more frequently associated with the T790M mutation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard treatments for non-small-cell lung cancer (NSCLC) with EGFR mutations.
- The T790M point mutation in EGFR exon 20 is the primary cause of acquired resistance to EGFR-TKIs.
- Understanding resistance mechanisms is crucial for optimizing NSCLC treatment strategies.
Purpose of the Study:
- To investigate the association between T790M mutation status and disease progression patterns in advanced NSCLC patients who failed initial EGFR-TKI therapy.
- To determine if specific patterns of tumor progression correlate with the emergence of the T790M resistance mutation.
Main Methods:
- Retrospective review of 181 advanced NSCLC patients with EGFR mutations who experienced treatment failure with first-generation EGFR-TKIs (gefitinib, erlotinib, afatinib).
- Evaluation of T790M mutation status via re-biopsy after initial EGFR-TKI failure.
- Analysis of patient characteristics, initial treatment response, T790M status, subsequent treatments, and progression patterns (solitary vs. multiple lesion progression).
Main Results:
- The T790M mutation was detected in 48% (87/181) of patients post-EGFR-TKI failure.
- Solitary lesion progression occurred in 40% of patients, while multiple lesion progression was observed in 60%.
- T790M mutation prevalence was significantly higher in patients with solitary lesion progression (58%) compared to multiple lesion progression (24%; P < .0001).
- Patients acquiring T790M showed better initial overall response rates (80% vs. 60%) and progression-free survival (11.4 vs. 9.3 months) on initial EGFR-TKIs compared to those without T790M.
Conclusions:
- Progression patterns during initial EGFR-TKI treatment are significantly associated with the development of the T790M resistance mutation.
- Initial EGFR-TKI response also correlates with T790M mutation status, suggesting a complex interplay between treatment efficacy and resistance mechanisms.
- These findings highlight the importance of monitoring progression patterns to potentially predict or understand T790M acquisition in NSCLC patients.
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