ArticleFrontiers in oncology2022
The Lifted Veil of Uncommon EGFR Mutation p.L747P in Non-Small Cell Lung Cancer: Molecular Feature and Targeting Sensitivity to Tyrosine Kinase Inhibitors.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Efficacy of TKIs in non-small cell lung cancer with atypical EGFR p.L747P and p.L747S mutations.Frontiers in oncology · 2026Article
- Dacomitinib in Combination with chemotherapy is effective in lung adenocarcinoma with rareFrontiers in oncology · 2026Article
- Targeting ErbB and tankyrase1/2 prevent the emergence of drug-tolerant persister cells in ALK-positive lung cancer.NPJ precision oncology · 2024Article
- Comparison between next-generation sequencing and multiplex polymerase chain reaction assays for nonsmall-cell lung cancer molecular diagnosis.Cancer medicine · 2024Article
- EGFR Tyrosine Kinase Inhibitors for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Podcast.Targeted oncology · 2023Article
- The treatment of patients with non-small cell lung cancer carrying uncommonTranslational cancer research · 2023Review
- Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations.Nature communications · 2022Article
- Durable response to afatinib rechallenge in a long-term survivor of non-small cell lung cancer harboring EGFR L858R and L747V mutations.Thoracic cancer · 2022Article
- Rapid Determination of 9 Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma in Human Plasma by QuEChERS-UPLC-MS/MS.Frontiers in pharmacology · 2022Article
- Case Report: Dacomitinib is effective in lung adenocarcinoma with rare EGFR mutation L747P and brain metastases.Frontiers in oncology · 2022Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe uncommon p.L747P mutation in epidermal growth factor receptor (EGFR) exon 19 reveals to alter the response to tyrosine kinase inhibitors (TKIs) in patients diagnosed with advanced non-small cell lung cancer (NSCLC). However, the underlying mechanism is still not clear. This study aimed to investigate the clinical outcomes, binding affinities, and modes of action of currently available EGFR TKIs towards p.L747P mutation. MATERIALS AND
methodsClinical data of NSCLC patients harboring p.L747P mutation who had received different generations of EGFR TKIs were collected from medical records. Computational structure of p.L747P was constructed and
resultsA total of five metastatic NSCLC patients with p.L747P mutation were included in the final analysis. Patients treated with second-generation (2G) TKI afatinib achieved numerically longer progression-free survival (range 2.4-8.5 months) than that with first-generation (1G, range 1.4-5.5 months) or third-generation (3G, range 1.6-7.5 months) TKIs. None of the patients administered 1G or 3G TKIs achieved tumor response, but two-thirds of them treated with afatinib achieved partial response. Dynamics simulation predicted that 2G TKIs presented the best binding affinity to p.L747P mutation. The cellular kinase inhibition assay and mice xenograft experiment confirmed that afatinib could potently inhibit p.L747P-mutant cells and significantly reduce p.L747P-mutant tumor growth (
conclusionsThe uncommon p.L747P mutation in EGFR exon 19 resulted in a poor response to first-generation EGFR TKIs. Afatinib revealed a better clinical response and binding affinity compared with osimertinib for this specific alteration.
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