ArticleBritish journal of cancer2021
Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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
43 citing papers in PubMed, 68 citations in OpenAlex.
- Biomarker Analysis of the Phase III NALA Study of Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with Previously Treated Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- AKAP13 regulates GLI1/ULK1 axis and drive tumor resistance to next-generation HER2-targeted therapies.Oncogene · 2026Article
- The actionable transcriptome: a framework for incorporating RNA sequencing into precision oncology.Nature reviews. Clinical oncology · 2026Review
- Genetically Encoded SpyTag Enables Modular AAV Retargeting via SpyCatcher-Fused Ligands for Targeted Gene Delivery.ACS synthetic biology · 2026Article
- Comparative profiling of osimertinib and fourth-generation EGFR inhibitors on EGFR-mutant proteins and cell lines.Frontiers in oncology · 2026Article
- High-throughput characterization of 5886 HER2 variants identifies 112 new in cellulo gain-of-function mutations.Genomics · 2025Article
- Synthesis and Absolute Configuration of the Sesquiterpene Lactone EPD, a Natural Product with Broad Antitumor Cell Activity via a Unique Mechanism of Action.Journal of natural products · 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
- New Gain-of-Function Mutations Prioritize Mechanisms of HER2 Activation.medRxiv : the preprint server for health sciences · 2025Article
- Impacts of genomic alterations on the efficacy of HER2-targeted antibody-drug conjugates in patients with metastatic breast cancer.Journal of translational medicine · 2025Article
- Pre-Clinical Rationale for Amcenestrant Combinations in HER2+/ER+ Breast Cancer.International journal of molecular sciences · 2025Article
- Nanotechnology Platform for the Delivery of Docetaxel and Tyrosine Kinase Inhibitors for HER2-Positive Breast Cancer Therapy.Pharmaceutical nanotechnology · 2025Article
- Combined cellular and biochemical profiling of Bruton's tyrosine kinase inhibitor nemtabrutinib reveals potential application in MAPK-driven cancers.Frontiers in oncology · 2025Article
- Neratinib plus dasatinib is highly synergistic in HER2-positive breast cancer in vitro and in vivo.Translational oncology · 2024Article
- Advances in the treatment of human epidermal growth factor receptor 2-positive gastric cancer.International journal of clinical oncology · 2024Review
- Enhanced anti-tumor effects by combination of tucatinib and radiation in HER2-overexpressing human cancer cell lines.Cancer cell international · 2024Article
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- Unleashing the power of anti-HER2 therapies in metastatic colorectal cancer: paving the way for a brighter future.ESMO gastrointestinal oncology · 2024Review
- PRESSING Need of Precision Care in HER2-Positive Colorectal Cancer: The ELEPHANT in the Room.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Treatment options for HER2-expressing colorectal cancer: updates and recent approvals.Therapeutic advances in medical oncology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman epidermal growth factor 2 (HER2/ERBB2) is frequently amplified/mutated in cancer. The tyrosine kinase inhibitors (TKIs) lapatinib, neratinib, and tucatinib are FDA-approved for the treatment of HER2-positive breast cancer. Direct comparisons of the preclinical efficacy of the TKIs have been limited to small-scale studies. Novel biomarkers are required to define beneficial patient populations.
methodsIn this study, the anti-proliferative effects of the three TKIs were directly compared using a 115 cancer cell line panel. Novel TKI response/resistance markers were identified through cross-analysis of drug response profiles with mutation, gene copy number and expression data.
resultsAll three TKIs were effective against HER2-amplified breast cancer models; neratinib showing the most potent activity, followed by tucatinib then lapatinib. Neratinib displayed the greatest activity in HER2-mutant and EGFR-mutant cells. High expression of HER2, VTCN1, CDK12, and RAC1 correlated with response to all three TKIs. DNA damage repair genes were associated with TKI resistance. BRCA2 mutations were correlated with neratinib and tucatinib response, and high expression of ATM, BRCA2, and BRCA1 were associated with neratinib resistance.
conclusionsNeratinib was the most effective HER2-targeted TKI against HER2-amplified, -mutant, and EGFR-mutant cell lines. This analysis revealed novel resistance mechanisms that may be exploited using combinatorial strategies.
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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.