ArticleOncotarget2015
Molecular determinants of drug-specific sensitivity for epidermal growth factor receptor (EGFR) exon 19 and 20 mutants in non-small cell lung cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Therapeutic exploration of uncommon EGFR exon 20 insertion mutations in advanced non-small cell lung cancer: breaking through brambles and thorns.Journal of cancer research and clinical oncology · 2022Pooled it
- [EGFR Exon 20 Insertion Mutation: Research Status and New Treatment Strategies].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- Review
- Non-small Cell Lung Cancer with EGFR or HER2 Exon 20 Insertion Mutations: Diagnosis and Treatment Options.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- Amivantamab for the treatment ofExpert review of anticancer therapy · 2022Article
- EGFR and HER2 exon 20 insertions in solid tumours: from biology to treatment.Nature reviews. Clinical oncology · 2022Review
- Cetuximab in Patients with Non-Small Cell Lung Cancer and EGFR Exon 20 Insertion Alterations.Clinical oncology, case reports · 2022Article
- A Rare Presentation of a Non-Asian Female With Metastatic Non-small-cell Lung Cancer HarboringAnticancer research · 2022Article
- Article
- New therapeutic approaches to overcoming resistant EGFR exon 20 alterations.Critical reviews in oncology/hematology · 2020Review
- EGFR exon 20 insertion mutations in non-small cell lung cancer.Translational cancer research · 2020Review
- Revisiting Epidermal Growth Factor Receptor (JCO precision oncology · 2019Article
- Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2018Article
- Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer.Nature medicine · 2018Article
- Exon 19 L747P mutation presented as a primary resistance to EGFR-TKI: a case report.Journal of thoracic disease · 2016Article
- Design, biological evaluation and 3D QSAR studies of novel dioxin-containing pyrazoline derivatives with thiourea skeleton as selective HER-2 inhibitors.Scientific reports · 2016Article
- Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay.Oncotarget · 2016Article
- EGFRvIII/integrin β3 interaction in hypoxic and vitronectinenriching microenvironment promote GBM progression and metastasis.Oncotarget · 2016Article
- Article
- Molecular inimitability amongst tumors: implications for precision cancer medicine in the age of personalized oncology.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
We hypothesized that aberrations activating epidermal growth factor receptor (EGFR) via dimerization would be more sensitive to anti-dimerization agents (e.g., cetuximab). EGFR exon 19 abnormalities (L747_A750del; deletes amino acids LREA) respond to reversible EGFR kinase inhibitors (TKIs). Exon 20 in-frame insertions and/or duplications (codons 767 to 774) and T790M mutations are clinically resistant to reversible/some irreversible TKIs. Their impact on protein function/therapeutic actionability are not fully elucidated.In our study, the index patient with non-small cell lung cancer (NSCLC) harbored EGFR D770_P772del_insKG (exon 20). A twenty patient trial (NSCLC cohort) (cetuximab-based regimen) included two participants with EGFR TKI-resistant mutations ((i) exon 20 D770>GY; and (ii) exon 19 LREA plus exon 20 T790M mutations). Structural modeling predicted that EGFR exon 20 anomalies (D770_P772del_insKG and D770>GY), but not T790M mutations, stabilize the active dimer configuration by increasing the interaction between the kinase domains, hence sensitizing to an agent preventing dimerization. Consistent with predictions, the two patients harboring D770_P772del_insKG and D770>GY, respectively, responded to an EGFR antibody (cetuximab)-based regimen; the T790M-bearing patient showed no response to cetuximab combined with erlotinib. In silico modeling merits investigation of its ability to optimize therapeutic selection based on structural/functional implications of different aberrations within the same gene.
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Registered trials
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