ArticleCell cycle (Georgetown, Tex.)2019
HER2-L755S mutation induces hyperactive MAPK and PI3K-mTOR signaling, leading to resistance to HER2 tyrosine kinase inhibitor treatment.
Article in Cell cycle (Georgetown, Tex.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The efficacy and safety of neoadjuvant buparlisib for breast cancer: A meta-analysis of randomized controlled studies.Medicine · 2019Pooled it
- Exome Sequencing Identifies Variants in MLH1 and ERBB2 as Potential Cancer-Predisposing Factors in Familial Early-Onset Colorectal Cancer.The Kaohsiung journal of medical sciences · 2026Article
- Review
- Comprehensive Molecular Docking and Molecular Dynamics Reveal Inhibitors of HER2 L755S, T798I, and T798M based on a Large Database of Curcumin Derivatives.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Next-generation sequencing identifies potential mechanisms of primary resistance to trastuzumab-containing therapies in HER2-positive gastric cancer: Analysis based on real-world data and online databases.Human vaccines & immunotherapeutics · 2025Article
- Dissecting endometrial cancer complexity in response to standard and targeted therapies.Cell death & disease · 2025Article
- High-throughput characterization of 5886 HER2 variants identifies 112 new in cellulo gain-of-function mutations.Genomics · 2025Article
- New Gain-of-Function Mutations Prioritize Mechanisms of HER2 Activation.medRxiv : the preprint server for health sciences · 2025Article
- Computational molecular insights into ibrutinib as a potent inhibitor of HER2-L755S mutant in breast cancer: gene expression studies, virtual screening, docking, and molecular dynamics analysis.Frontiers in molecular biosciences · 2025Article
- Circulating tumor cells: indicators of cancer progression, plasticity and utility for therapies.Pathology oncology research : POR · 2025Review
- Analysis of methylation features associated with neoadjuvant efficacy in HER2-positive breast cancer.Frontiers in oncology · 2025Article
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- HER2 mutation as an emerging target in advanced breast cancer.Cancer science · 2024Review
- RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers.International journal of molecular sciences · 2024Review
- Resistance mechanisms and prospects of trastuzumab.Frontiers in oncology · 2024Review
- Exosomal Linc00969 induces trastuzumab resistance in breast cancer by increasing HER-2 protein expression and mRNA stability by binding to HUR.Breast cancer research : BCR · 2023Article
- Resistance to anti-HER2 therapy associated with the TSC2 nonsynonymous variant c.4349 C > G (p.Pro1450Arg) is reversed by CDK4/6 inhibitor in HER2-positive breast cancer.NPJ breast cancer · 2023Article
- Variant calling enhances the identification of cancer cells in single-cell RNA sequencing data.PLoS computational biology · 2022Article
- A novel 7 RNA-based signature for prediction of prognosis and therapeutic responses of wild-type BRAF cutaneous melanoma.Biological procedures online · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
L755S, a HER2 kinase domain mutation, is the most common HER2 mutation in breast cancer associated with resistance to anti-HER2 trastuzumab treatment. Here, we showed that HER2-L755S confers hyperactivation of MAPK and PI3K/AKT/mTOR pathways and resistance to both reversible and irreversible HER2 tyrosine kinase inhibitors. We further demonstrated that the HER2 TKIs in combination with MEK inhibitor, AZD6244, or PI3K inhibitor, GDC0941, yield robust killing in HER2-L755S cancer cells, indicating a novel targeted strategy to overcome HER2-L755S resistance to anti-HER2 treatment.
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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.