ArticleNeuro-oncology2016
Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel.
Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- Review
- Astrocyte Reprogramming Drives Tumor Progression and Chemotherapy Resistance in Agent-Based Models of Breast Cancer Brain Metastases.Bulletin of mathematical biology · 2025Article
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- Astrocyte involvement in brain metastasis: from biological mechanisms to therapeutic strategies.Cancer metastasis reviews · 2025Review
- Brain microenvironment orchestrates highly aggressive tumor variants: current trends and therapeutic approaches.Frontiers in aging neuroscience · 2025Review
- Analysis of neuroglia and immune cells in the tumor microenvironment of breast cancer brain metastasis.Cancer biology & therapy · 2024Review
- Identification of New Chemoresistance-Associated Genes in Triple-Negative Breast Cancer by Single-Cell Transcriptomic Analysis.International journal of molecular sciences · 2024Article
- A Double Regression Method for Graphical Modeling of High-dimensional Nonlinear and Non-Gaussian Data.Statistics and its interface · 2024Article
- The EDN1/EDNRA/β‑arrestin axis promotes colorectal cancer progression by regulating STAT3 phosphorylation.International journal of oncology · 2023Article
- The progress of microenvironment-targeted therapies in brain metastases.Frontiers in molecular biosciences · 2023Review
- Tumor Immune Microenvironment of Brain Metastases: Toward Unlocking Antitumor Immunity.Cancer discovery · 2022Review
- Glutamatergic Neurons in the Amygdala Are Involved in Paclitaxel-Induced Pain and Anxiety.Frontiers in psychiatry · 2022Article
- Macitentan improves antitumor immune responses by inhibiting the secretion of tumor-derived extracellular vesicle PD-L1.Theranostics · 2022Article
- Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.Pharmaceutics · 2021Review
- YAP and endothelin-1 signaling: an emerging alliance in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Targeting the endothelin axis as a therapeutic strategy for oral cancer metastasis and pain.Scientific reports · 2020Article
- Endothelin Receptor Antagonists: Status Quo and Future Perspectives for Targeted Therapy.Journal of clinical medicine · 2020Review
- Markov Neighborhood Regression for High-Dimensional Inference.Journal of the American Statistical Association · 2020Article
- Connexins in Lung Cancer and Brain Metastasis.Frontiers in oncology · 2020Review
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10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundWe recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases.
methodsThe effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy.
resultsCancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases.
conclusionsDual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with 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.