ArticleCancer discovery2015
EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
75 citing papers in PubMed, 120 citations in OpenAlex.
- 5' Rapid Amplification of cDNA Ends (5' RACE)-Based Targeted RNA Sequencing Assay for the Analysis of Clinically Relevant Alterations in Lung Cancer Patients.International journal of molecular sciences · 2026Article
- Acquired Resistance to Afatinib Mediated by EGFR T790M in Lung Adenocarcinoma Patients Harboring EGFR-KDD: A Case Report and Literature Review.Current oncology (Toronto, Ont.) · 2026Review
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Congenital mesoblastic nephroma: a single-center retrospective study.Translational pediatrics · 2026Article
- Article
- Combined treatment of TKIs with Cilengitide overcomes afatinib-resistance in EGFR-mutated NSCLC cells.Molecular biology reports · 2025Article
- Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods.Biophysical journal · 2025Review
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Adjunctive diagnostic tool for histopathological classification of congenital mesoblastic nephroma based in molecular genetic findings.Journal of cancer research and clinical oncology · 2025Article
- Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors.The oncologist · 2025Article
- Epidermal Growth Factor Receptor Kinase Domain Duplication in Lung Adenocarcinoma with Sensitive Response to Afatinib: A Case Report and Literature Review.Lung Cancer (Auckland, N.Z.) · 2025Article
- Advances in Synthetic Lethality in Potential Oncology Therapeutic Approaches.Current topics in medicinal chemistry · 2025Review
- Clinical and Radiographic Benefit of a Patient With Metastatic Non-Small Cell Lung Cancer Harboring anJCO precision oncology · 2024Article
- Comprehensive mutational scanning of EGFR reveals TKI sensitivities of extracellular domain mutants.Nature communications · 2024Article
- Intragenic Rearrangement Burden Associates with Immune Cell Infiltration and Response to Immune Checkpoint Blockade in Cancer.Cancer immunology research · 2024Article
- A Constitutive EGFR Kinase Dimer to Study Inhibitor Pharmacology.Molecular pharmacology · 2024Article
- EGFR kinase domain duplication in lung adenocarcinoma with systemic and intracranial response to a double-dose of furmonertinib: a case report and literature review.Frontiers in oncology · 2024Article
- Article
- An Overview of EGFR Mechanisms and Their Implications in Targeted Therapies for Glioblastoma.International journal of molecular sciences · 2023Review
- Amuvatinib Blocks SARS-CoV-2 Infection at the Entry Step of the Viral Life Cycle.Microbiology spectrum · 2023Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledOncogenic EGFR mutations are found in 10% to 35% of lung adenocarcinomas. Such mutations, which present most commonly as small in-frame deletions in exon 19 or point mutations in exon 21 (L858R), confer sensitivity to EGFR tyrosine kinase inhibitors (TKI). In analyzing the tumor from a 33-year-old male never-smoker, we identified a novel EGFR alteration in lung cancer: EGFR exon 18-25 kinase domain duplication (EGFR-KDD). Through analysis of a larger cohort of tumor samples, we detected additional cases of EGFR-KDD in lung, brain, and other cancers. In vitro, EGFR-KDD is constitutively active, and computational modeling provides potential mechanistic support for its auto-activation. EGFR-KDD-transformed cells are sensitive to EGFR TKIs and, consistent with these in vitro findings, the index patient had a partial response to the EGFR TKI afatinib. The patient eventually progressed, at which time resequencing revealed an EGFR-dependent mechanism of acquired resistance to afatinib, thereby validating EGFR-KDD as a driver alteration and therapeutic target. SIGNIFICANCE: We identified oncogenic and drug-sensitive EGFR-KDD that is recurrent in lung, brain, and soft-tissue cancers and documented that a patient with metastatic lung adenocarcinoma harboring the EGFR-KDD derived significant antitumor response from treatment with the EGFR inhibitor afatinib. Findings from these studies will be immediately translatable, as there are already several approved EGFR inhibitors in clinical use.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.