EGFR L858M/L861Q cis Mutations Confer Selective Sensitivity to Afatinib
Jamie A Saxon1, Lynette M Sholl2, Pasi A Jänne3
1Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Summary
Afatinib shows promise for lung cancer patients with rare EGFR mutations, unlike other tyrosine kinase inhibitors (TKIs). This study investigated the efficacy of TKIs against uncommon EGFR mutations in vitro.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Tyrosine kinase inhibitors (TKIs) are used for EGFR-mutant lung cancers.
- Efficacy of TKIs against uncommon EGFR mutations is not well understood.
Observation:
- A patient with non-small cell lung cancer (NSCLC) had EGFR L858M/L861Q mutations in cis.
- The patient showed resistance to erlotinib but responded to afatinib.
- In vitro, EGFR L858M/L861Q cells were less responsive to first- and third-generation TKIs compared to EGFR L858R cells.
Findings:
- Afatinib effectively inhibited proliferation and EGFR phosphorylation in both EGFR L858M/L861Q and EGFR L858R mutant cells.
- First- and third-generation TKIs showed reduced efficacy against EGFR L858M/L861Q mutations.
Implications:
- Afatinib may be a viable treatment for lung cancer patients with specific rare EGFR mutations.
- Further research into how uncommon mutations impact TKI binding is crucial for developing targeted therapies.
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