ArticleCancer cell2018
Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations.
Article in Cancer cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.
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
104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Efficacy of anti-HER2 drugs in the treatment of patients with HER2-mutated cancers: a systematic review and meta-analysis.Clinical and experimental medicine · 2023Pooled it
- Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Guideline
- Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.Nature medicine · 2025Trial
- HER2 Alterations in Squamous Cell Lung Cancer: Biology, Therapeutic Landscape, and Emerging Precision Approaches.Cancers · 2026Review
- Molecular heterogeneity of ERBB2-altered cancers: A pan-cancer landscape across US and Japanese cohorts.NPJ precision oncology · 2026Article
- HER2-specific synthetic antigen receptor T cell therapy synergizes with radiotherapy to provide improved antitumor efficacy in non-small cell lung cancer.Journal of leukocyte biology · 2026Article
- ERBB2 I655V mutation correlates with efficacy of immunotherapy in gallbladder cancer.World journal of surgical oncology · 2026Article
- HER2 and urothelial carcinoma: current understanding and future directions.Nature reviews. Urology · 2026Review
- Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer.Cancer discovery · 2026Article
- Evolving treatment strategies for HER2-altered non-small-cell lung cancer: the rise of TKIs and ADCs.Frontiers in oncology · 2026Review
- Hepatic metastasis of mucinous adenocarcinoma with neuroendocrine differentiation harboring a rare HER2 R678Q mutation: a case report and literature review.Frontiers in oncology · 2026Article
- Molecular Alterations and Pathways in Intrahepatic Cholangiocarcinoma: Available Evidence and New Perspectives.International journal of molecular sciences · 2025Review
- Successful treatment of gynecologic malignancy with trastuzumab deruxtecan in three patients withGynecologic oncology reports · 2025Article
- A paired sequencing study of goblet cell adenocarcinomas with coincident sessile serrated lesions and low-grade appendiceal mucinous neoplasms.Virchows Archiv : an international journal of pathology · 2025Article
- Risk of central nervous system metastasis and survival in HER2+ positive breast and non-breast cancers.Neuro-oncology practice · 2025Article
- Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods.Biophysical journal · 2025Review
- High-throughput characterization of 5886 HER2 variants identifies 112 new in cellulo gain-of-function mutations.Genomics · 2025Article
- Beyond borders: engineering organ-targeted immunotherapies to overcome site-specific barriers in cancer.Drug delivery and translational research · 2025Review
- Mutational Landscape Assessed in Tumor Tissue and Circulating Tumor DNA During Treatment of Patients with HER2/ERBB2-Mutated Solid Tumors.BMC cancer · 2025Article
- Potential Resistance to Oxaliplatin-Based Regimens in Gastric Cancer Patients with ERBB2 R678Q Mutation: Evidence from a National Genomic Database.Current issues in molecular biology · 2025Article
44 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
34 authors at 7 institutions in 2 countries.
Funding
Abstract
Deregulated HER2 is a target of many approved cancer drugs. We analyzed 111,176 patient tumors and identified recurrent mutations in HER2 transmembrane domain (TMD) and juxtamembrane domain (JMD) that include G660D, R678Q, E693K, and Q709L. Using a saturation mutagenesis screen and testing of patient-derived mutations we found several activating TMD and JMD mutations. Structural modeling and analysis showed that the TMD/JMD mutations function by improving the active dimer interface or stabilizing an activating conformation. Further, we found that HER2 G660D employed asymmetric kinase dimerization for activation and signaling. Importantly, anti-HER2 antibodies and small-molecule kinase inhibitors blocked the activity of TMD/JMD mutants. Consistent with this, a G660D germline mutant lung cancer patient showed remarkable clinical response to HER2 blockade.
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.