ArticleCancer medicine2019
Targeting of the HER2/HER3 signaling axis overcomes ligand-mediated resistance to trastuzumab in HER2-positive breast cancer.
Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 3 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
49 citing papers in PubMed, 3 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- [Clinical Progress and Prospects of Antibody-drug Conjugates in Advanced NSCLC].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Pooled it
- Investigating the Co-Expression Rate of HER2 and HER3 Biomarkers in Cancer Patients: A Systematic Review and Meta-Analysis.Asian Pacific journal of cancer prevention : APJCP · 2024Pooled it
- Intercepting Premalignant, Preinvasive Breast Lesions Through Vaccination.Frontiers in immunology · 2021Pooled it
- A Dual Role for the Placenta and Human Amniotic Epithelial Cells in HER3-Targeted Nanotherapy.Research square · 2026Article
- Evolving antibody-drug conjugates in breast cancer from precision delivery to tumor microenvironment reprogramming.Journal of hematology & oncology · 2026Review
- HER3 upregulation reduces DS-8201 sensitivity in HER2-positive tumor cells by ATR/CHK1/FoxO1 signaling cascade.Acta pharmacologica Sinica · 2026Article
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway.Genes & diseases · 2025Review
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Potential of epithelial membrane protein 3 as a novel therapeutic target for human breast cancer.Oncology reports · 2025Article
- Review
- Article
- Disrupting EGFR-HER2 Transactivation by Pertuzumab in HER2-Positive Cancer: Quantitative Analysis Reveals EGFR Signal Input as Potential Predictor of Therapeutic Outcome.International journal of molecular sciences · 2024Article
- Targeted dual degradation of HER2 and EGFR obliterates oncogenic signaling, overcomes therapy resistance, and inhibits metastatic lesions in HER2-positive breast cancer models.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Cancer treatment with biosimilar drugs: A review.Cancer innovation · 2024Review
- Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies.Journal of clinical medicine · 2024Review
- Prognostic value of baseline neutrophil/lymphocyte ratio in HER2-positive metastatic breast cancer: exploratory analysis of data from the CLEOPATRA trial.Breast cancer research : BCR · 2024Article
- Resistance mechanisms and prospects of trastuzumab.Frontiers in oncology · 2024Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2-targeted therapy, especially the anti-HER2 antibody trastuzumab, is standard for HER2-positive breast cancer; however, its efficacy is limited in a subpopulation of patients. HER3 ligand (heregulin)-dependent HER2-HER3 interactions play a critical role in the evasion of apoptosis and are therefore a target for oncotherapy to treat HER2-positive breast cancer. The anti-HER2 antibody pertuzumab and anti-HER3 antibody patritumab both target this heregulin-HER3-HER2 complex in different ways. This study examined the anticancer efficacy of dual HER2 and HER3 blockade in trastuzumab-resistant HER2-positive breast cancer. HER2-positive SKBR3 or BT474 cells overexpressing heregulin (SKBR3-HRG, BT474-HRG) were used to evaluate the efficacy of trastuzumab, pertuzumab, and patritumab in vitro by performing cell viability, immunoblotting, and clonogenic assays. The effects of these agents were then evaluated in vivo using BT474-HRG and an intrinsic heregulin-expressing and HER2-positive JIMT-1 xenograft models. SKBR3-HRG and BT474-HRG cells lost sensitivity to trastuzumab, which was accompanied by Akt activation. Unexpectedly, trastuzumab in combination with pertuzumab or patritumab also showed limited efficacy toward these cells. In contrast, trastuzumab/pertuzumab/patritumab triple treatment demonstrated potent anticancer efficacy, concomitant with strong repression of Akt. Finally, in heregulin-expressing BT474-HRG and JIMT-1 xenograft models, the addition of pertuzumab and patritumab to trastuzumab also enhanced antitumor efficacy leading to tumor regression. The current study found that triple blockade of HER2 and HER3 using trastuzumab, pertuzumab, and patritumab could overcome resistance to trastuzumab therapy in heregulin-expressing and HER2-positive breast cancer, which could be exploited clinically.
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.