ArticleClinical cancer research : an official journal of the American Association for Cancer Research2018
EGFR Exon 20 Insertion Mutations Display Sensitivity to Hsp90 Inhibition in Preclinical Models and Lung Adenocarcinomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01854034 (Phase II Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR), which is not on this map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Phase II Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 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
- Erlotinib and Onalespib Lactate Focused on EGFR Exon 20 Insertion Non-Small Cell Lung Cancer (NSCLC): A California Cancer Consortium Phase I/II Trial (NCI 9878).Clinical lung cancer · 2021Trial
- Gallic Acid Enhances the Anticancer Activity of Docetaxel in Triple-Negative Breast Cancer Cells.Biology · 2026Article
- Elevated plasma HSP90α as a prognostic marker in EGFR-mutant non-small cell lung cancer.Oncology letters · 2025Article
- Current paradigm of EGFRMed (New York, N.Y.) · 2025Review
- Efficacy of EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer with EGFR exon 19 insertions: clinical-genomic, preclinical analysis through LC-SCRUM-Asia (multi-institutional genomic screening registry).Lung cancer (Amsterdam, Netherlands) · 2025Article
- Potential benefits of combined treatment with Hsp90 inhibitor AUY922 and cisplatin for overcoming drug resistance in nasopharyngeal carcinoma.American journal of cancer research · 2025Article
- A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition.NPJ precision oncology · 2024Article
- The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors.JTO clinical and research reports · 2024Article
- The current landscape, advancements, and prospects in the treatment of patients with EGFR exon 20 insertion mutations warrant scientific elucidation.Frontiers in oncology · 2024Review
- Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non-small cell lung cancer.Thoracic cancer · 2023Review
- Review
- EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors.Lung cancer (Amsterdam, Netherlands) · 2023Article
- Dose-escalation trial of combination dabrafenib, trametinib, and AT13387 in patients with BRAF-mutant solid tumors.Cancer · 2023Article
- The EGFR C797S Mutation Confers Resistance to a Novel EGFR Inhibitor CLN-081 to EGFR Exon 20 Insertion Mutations.JTO clinical and research reports · 2023Article
- EGFR exon 20 insertion mutations in advanced non-small-cell lung cancer: current status and perspectives.Biomarker research · 2022Review
- Review
- EGFR and HER2 exon 20 insertions in solid tumours: from biology to treatment.Nature reviews. Clinical oncology · 2022Review
- Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations.OncoTargets and therapy · 2022Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeEXPERIMENTAL
designPreclinical models of a representative set of EGFR exon 20 insertion mutations to evaluate the efficacy of different inhibitors and description of the clinical outcome of an advanced lung cancer.
resultsWe show that select first-, second-, and third-generation EGFR inhibitors are unable to deter common EGFR exon 20 insertion mutants in concentrations that spare the wild-type kinase. Nonetheless, EGFR exon 20 insertion mutants associate with the Hsp90 chaperone system. We exploit this vulnerability to show that the nongeldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets, and induces apoptosis. In addition, a patient whose EGFR inhibitor-insensitive lung adenocarcinoma harbored an
conclusionsThe report confirms that EGFR exon 20 mutations are dependent on Hsp90 and are readily inhibited by the Hsp90 inhibitor luminespib; a treatment strategy that has been pursued in a confirmatory clinical trial (NCT01854034) for this group of lung adenocarcinomas that currently represent an unmet clinical need in precision oncology.
Indexed as
Identifiers
What OpenQuestion holds
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.