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Published on: August 11, 2017
Association between advanced NSCLC T790 M EGFR-TKI secondary resistance and prognosis: A observational study
Yuli Wang1, Yuan Wei, Xiaoping Ma
1The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi Changji Branch Hospital, the First Affiliated Hospital of Xinjiang Medical University, Changji School of Medicine, Shihezi University, Shihezi, Xinjiang, China.
Abstract:
Epidermal growth factor receptor (EGFR) mutations for EGFR-tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients are with clinical benefits. Nevertheless, eventual resistance to EGFR-TKI is almost inevitable. In about 50% patients, EGFR-TKI develops a secondary mutation, which is often the T790 M mutation. We aimed to investigate the relationship between EGFR gene status in the peripheral blood and prognosis (progression-free survival [PFS] and overall survival [OS]) in advanced lung adenocarcinoma patients and the 20 exon 790 site mutation (T790 M) and acquired resistance to EGFR-TKI.A total of 49 patients with EGFR-TKI resistance and advanced lung cancer who visited the Shihezi University School of Medicine between 12/2013 and 12/2014 were enrolled in this study. Peripheral blood plasma DNA was isolated after EGFR-TKI resistance and the EGFR exon 20 T790 M mutation was detected using the probe amplification refractory mutation system method.The T790 M mutation rate was 30.6% (15/49). There was no association between T790 M mutation and age, gender, smoking, clinical stage, Eastern Cooperative Oncology Group rating, initial EGFR mutation, and EGFR-TKI drugs, but EGFR-TKI resistance was associated with progression (P = .009). Median progression-free survival (PFS) of patients with T790 M mutation was 9.6 months and median overall survival (OS) was 17.6 months, compared to 6.8 and 12.7 months in controls (P = .018 and P = .027). Multivariate analysis showed that T790 M mutations independently affected the PFS (risk ratio, RR = 0.653, 95% confidence interval, CI: 0.069-0.886, P = .032) and OS (RR = 0.847, 95% CI: 0.208-2.696, P = .008).T790 M mutation and EGFR-TKI resistance are independent factors to affect PFS and OS of non-small cell lung cancer patients.
Insights
The T790M mutation in EGFR-TKI resistant non-small cell lung cancer patients is linked to better progression-free survival and overall survival. This finding highlights the T790M mutation as an independent prognostic factor in advanced lung adenocarcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) mutations predict benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC).
- Acquired resistance to EGFR-TKI is common, often due to secondary mutations like T790M.
Purpose of the Study:
- To investigate the prognostic significance of EGFR gene status in peripheral blood for patients with advanced lung adenocarcinoma.
- To determine the association between the T790M mutation and acquired resistance to EGFR-TKI, and its impact on patient outcomes.
Main Methods:
- A cohort of 49 patients with EGFR-TKI resistance and advanced lung cancer was studied.
- Peripheral blood plasma DNA was analyzed for the EGFR T790M mutation using the probe amplification refractory mutation system.
Main Results:
- The T790M mutation was detected in 30.6% of patients.
- Patients with the T790M mutation showed significantly longer median progression-free survival (9.6 months) and overall survival (17.6 months) compared to controls.
- Multivariate analysis confirmed T790M mutations as independent predictors of improved PFS and OS.
Conclusions:
- The T790M mutation is an independent prognostic factor for progression-free survival and overall survival in non-small cell lung cancer patients with EGFR-TKI resistance.
- EGFR gene status in peripheral blood can provide valuable prognostic information for advanced lung adenocarcinoma.
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