ArticleOncotarget2013
Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 162 citations in OpenAlex.
- Targeting Ferroptosis as the Achilles' Heel of Breast Cancer: Mechanisms and Therapeutic Opportunities from a Comprehensive Systematic Review.International journal of molecular sciences · 2025Pooled it
- Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials.Clinical drug investigation · 2019Pooled it
- Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens.Breast cancer research and treatment · 2021Trial
- PIK3CA alterations and benefit with neratinib: analysis from the randomized, double-blind, placebo-controlled, phase III ExteNET trial.Breast cancer research : BCR · 2019Trial
- Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU.Clinical drug investigation · 2019Trial
- Exploring tyrosine kinase inhibitors for HER2-positive breast cancer: comprehensive review on a complete pharmacology-molecular mechanisms, safety profiles, and insights from preclinical and clinical studies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Targeted Therapies for Each Subtype of Breast Cancer.MedComm · 2026Review
- Advances in Targeting HER2 across Cancer Subtypes: A Pan-Tumor Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Increased Antiproliferative Activity of Antiestrogens and Neratinib Treatment by Calcitriol in HER2-Positive Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Facing the Challenge to Mimic Breast Cancer Heterogeneity: Established and Emerging Experimental Preclinical Models Integrated with Omics Technologies.International journal of molecular sciences · 2025Review
- Diagnostic and therapeutic advances for HER2-expressing or amplified gynecologic cancers.Gynecologic oncology · 2025Review
- Pre-Clinical Rationale for Amcenestrant Combinations in HER2+/ER+ Breast Cancer.International journal of molecular sciences · 2025Article
- A phase Ib/II trial of neoadjuvant neratinib added to standard therapy in patients with HER2-positive or HR-positive/HER2-negative inflammatory breast cancer (including stage III and IV disease).Therapeutic advances in medical oncology · 2025Article
- Neratinib plus dasatinib is highly synergistic in HER2-positive breast cancer in vitro and in vivo.Translational oncology · 2024Article
- Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance.Nature reviews. Clinical oncology · 2024Review
- New Frontiers in the Treatment of Patients with HER2+ Cancer and Brain Metastases: Is Radiotherapy Always Useful?Cancers · 2024Review
- Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models.British journal of cancer · 2024Article
- Catalysts of Healing: A Symphony of Synthesis and Clinical Artistry in Small-Molecule Agents for Breast Cancer Alleviation.Molecules (Basel, Switzerland) · 2024Review
- Case report: Near-complete response to neratinib-based treatment in HR-positiveFrontiers in oncology · 2024Article
- Review
25 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
17 authors at 7 institutions in 3 countries.
Funding
Abstract
Trastuzumab has been shown to improve the survival outcomes of HER2 positive breast cancer patients. However, a significant proportion of HER2-positive patients are either inherently resistant or develop resistance to trastuzumab. We assessed the effects of neratinib, an irreversible panHER inhibitor, in a panel of 36 breast cancer cell lines. We further assessed its effects with or without trastuzumab in several sensitive and resistant breast cancer cells as well as a BT474 xenograft model. We confirmed that neratinib was significantly more active in HER2-amplified than HER2 non-amplified cell lines. Neratinib decreased the activation of the 4 HER receptors and inhibited downstream pathways. However, HER3 and Akt were reactivated at 24 hours, which was prevented by the combination of trastuzumab and neratinib. Neratinib also decreased pHER2 and pHER3 in acquired trastuzumab resistant cells. Neratinib in combination with trastuzumab had a greater growth inhibitory effect than either drug alone in 4 HER2 positive cell lines. Furthermore, trastuzumab in combination with neratinib was growth inhibitory in SKBR3 and BT474 cells which had acquired resistance to trastuzumab as well as in a BT474 xenograft model. Innately trastuzumab resistant cell lines showed sensitivity to neratinib, but the combination did not enhance response compared to neratinib alone. Levels of HER2 and phospho-HER2 showed a direct correlation with sensitivity to neratinib. Our data indicate that neratinib is an effective anti-HER2 therapy and counteracted both innate and acquired trastuzumab resistance in HER2 positive breast cancer. Our results suggest that combined treatment with trastuzumab and neratinib is likely to be more effective than either treatment alone for both trastuzumab-sensitive breast cancer as well as HER2-positive tumors with acquired resistance to trastuzumab.
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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.