ArticleNature cancer2022
Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Nonclinical and Clinical Assessments of an Optimized Tablet Formulation of the Novel HER2-Selective Tyrosine Kinase Inhibitor Zongertinib: Focus on Relative Bioavailability and Impact of Variation of Gastric pH.Molecular pharmaceutics · 2025Trial
- Relative Bioavailability of Zongertinib, an Orally Administered HER2-Selective Tyrosine Kinase Inhibitor, under Fed and Fasted Conditions in Healthy Male Participants: Results from Two Randomized, Open-Label, Crossover Studies.Molecular pharmaceutics · 2025Trial
- Recent advances in HER2-targeted inhibitors for cancer therapy.Pharmaceutical science advances · 2026Review
- Article
- In Silico Studies of Potent Tyrosine Kinase Inhibitors: Molecular Docking and Pharmacophore Modeling Approaches.Molecules (Basel, Switzerland) · 2026Article
- Nitrogen-containing FDA-approved drugs in 2025: synthesis, significance and therapeutic applications.RSC advances · 2026Review
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pharmacophore modeling and molecular dynamics simulations to study the conformational stability of natural HER2 inhibitors in breast cancer therapy.Molecular diversity · 2026Article
- Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer.Cancer discovery · 2026Article
- Chemical profiling andFrontiers in nutrition · 2026Article
- Beamion BCGC-1: phase Ib/II trial of zongertinib for advanced HER2-positive breast or gastroesophageal cancers.Future oncology (London, England) · 2025Article
- Using a Novel Consensus-Based Chemoinformatics Approach to Predict ADMET Properties and Druglikeness of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2025Review
- Warhead-bearing natural compounds for multi-pathway irreversible inhibition to overcome drug resistance in colorectal cancer.Medical oncology (Northwood, London, England) · 2025Article
- Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers.Cancer discovery · 2025Article
- HER2-Positive Breast Cancer Treatment and Resistance.Advances in experimental medicine and biology · 2025Review
- Article
- Network pharmacology, molecular docking and experimental approaches of the anti-proliferative effects ofHeliyon · 2024Article
- A Probe-Free Occupancy Assay to Assess a Targeted Covalent Inhibitor of Receptor Tyrosine-Protein Kinase erbB-2.ACS pharmacology & translational science · 2024Article
- CoHIT: a one-pot ultrasensitive ERA-CRISPR system for detecting multiple same-site indels.Nature communications · 2024Article
- Impact of camel milk lactoferrin peptides against breast cancer cells:Frontiers in pharmacology · 2024Article
Corrections and comments
- Commented on by
Authors and funding
43 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic alterations in human epidermal growth factor receptor 2 (HER2) occur in approximately 2% of patients with non-small cell lung cancer and predominantly affect the tyrosine kinase domain and cluster in exon 20 of the ERBB2 gene. Most clinical-grade tyrosine kinase inhibitors are limited by either insufficient selectivity against wild-type (WT) epidermal growth factor receptor (EGFR), which is a major cause of dose-limiting toxicity or by potency against HER2 exon 20 mutant variants. Here we report the discovery of covalent tyrosine kinase inhibitors that potently inhibit HER2 exon 20 mutants while sparing WT EGFR, which reduce tumor cell survival and proliferation in vitro and result in regressions in preclinical xenograft models of HER2 exon 20 mutant non-small cell lung cancer, concomitant with inhibition of downstream HER2 signaling. Our results suggest that HER2 exon 20 insertion-driven tumors can be effectively treated by a potent and highly selective HER2 inhibitor while sparing WT EGFR, paving the way for clinical translation.
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.