ArticleProceedings of the National Academy of Sciences of the United States of America2012
Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 154 citations in OpenAlex.
- Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases.Breast cancer research : BCR · 2020Trial
- Recombinant human endostatin combined with radiotherapy in the treatment of brain metastases of non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2014Trial
- Characterizing the effects of anti-PD1 immunotherapy on ataxia in a vestibular schwannoma mouse model.Journal of neuro-oncology · 2026Article
- Evaluating the Translation Value of TwoCancers · 2026Article
- Preclinical models of breast cancer metastasis: strengths, limitations, and clinical relevance.NPJ breast cancer · 2026Review
- NKG2D upregulation sensitizes tumors to combined anti-PD1 and anti-VEGF therapy and prevents hearing loss.Nature communications · 2026Article
- Novel anti-HER2 nanobody-drug conjugates with enhanced penetration of solid tumor and BBB, reduced systemic exposure and superior antitumor efficacy.Acta pharmacologica Sinica · 2026Article
- A cochlea-sparing strategy for non-invasive control of intracranial schwannomas via peripheral irradiation and anti-PD-1 therapy enhanced by STING activation.Theranostics · 2026Article
- Establishment and validation of an orthotopic brain metastasis tumor model in C57BL/6 mice.PeerJ · 2026Article
- Incidence and prognosis of brain metastases in esophageal carcinoma: a systematic review and meta-analysis.Journal of thoracic disease · 2025Article
- Solid Stress Estimations via Intraoperative 3D Navigation in Patients with Brain Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- RNF114 Interacts with EWSR1 to Regulate VEGFR2 in HER2-positive Breast Cancer.Journal of Cancer · 2025Article
- Programming tissue-sensing T cells that deliver therapies to the brain.Science (New York, N.Y.) · 2024Article
- Preclinical evaluation of targeted therapies for central nervous system metastases.Disease models & mechanisms · 2024Review
- The relationship between brain metastasis and HER2 expression status in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Combined inhibition of HER2 and VEGFR synergistically improves therapeutic efficacy via PI3K-AKT pathway in advanced ovarian cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities.Cancers · 2023Article
- miR-146a-5p Promotes Angiogenesis and Confers Trastuzumab Resistance in HER2+ Breast Cancer.Cancers · 2023Article
- Combination of radiotherapy and targeted therapy for HER2-positive breast cancer brain metastases.European journal of medical research · 2023Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Brain metastases are a serious obstacle in the treatment of patients with human epidermal growth factor receptor-2 (HER2)-amplified breast cancer. Although extracranial disease is controlled with HER2 inhibitors in the majority of patients, brain metastases often develop. Because these brain metastases do not respond to therapy, they are frequently the reason for treatment failure. We developed a mouse model of HER2-amplified breast cancer brain metastasis using an orthotopic xenograft of BT474 cells. As seen in patients, the HER2 inhibitors trastuzumab and lapatinib controlled tumor progression in the breast but failed to contain tumor growth in the brain. We observed that the combination of a HER2 inhibitor with an anti-VEGF receptor-2 (VEGFR2) antibody significantly slows tumor growth in the brain, resulting in a striking survival benefit. This benefit appears largely due to an enhanced antiangiogenic effect: Combination therapy reduced both the total and functional microvascular density in the brain xenografts. In addition, the combination therapy led to a marked increase in necrosis of the brain lesions. Moreover, we observed even better antitumor activity after combining both trastuzumab and lapatinib with the anti-VEGFR2 antibody. This triple-drug combination prolonged the median overall survival fivefold compared with the control-treated group and twofold compared with either two-drug regimen. These findings support the clinical development of this three-drug regimen for the treatment of HER2-amplified breast cancer brain metastases.
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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.