ArticleTranslational oncology2012
Antivascular therapy for multidrug-resistant ovarian tumors by macitentan, a dual endothelin receptor antagonist.
Article in Translational oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 31 citations in OpenAlex.
- Macitentan improves antitumor immune responses by inhibiting the secretion of tumor-derived extracellular vesicle PD-L1.Theranostics · 2022Article
- YAP and endothelin-1 signaling: an emerging alliance in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- β-arrestin1/YAP/mutant p53 complexes orchestrate the endothelin A receptor signaling in high-grade serous ovarian cancer.Nature communications · 2019Article
- Targeting Endothelin-1 Receptor/β-Arrestin-1 Axis in Ovarian Cancer: From Basic Research to a Therapeutic Approach.Frontiers in endocrinology · 2019Review
- Upregulation of Endothelin-1/Endothelin A Receptor Expression Correlates with Heparanase Expression in Ovarian Carcinoma.Iranian journal of medical sciences · 2018Article
- hMENA is a key regulator in endothelin-1/β-arrestin1-induced invadopodial function and metastatic process.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Blocking endothelin-1-receptor/β-catenin circuit sensitizes to chemotherapy in colorectal cancer.Cell death and differentiation · 2017Article
- β-arrestin1 at the cross-road of endothelin-1 signaling in cancer.Journal of experimental & clinical cancer research : CR · 2016Review
- Endothelin A receptor drives invadopodia function and cell motility through the β-arrestin/PDZ-RhoGEF pathway in ovarian carcinoma.Oncogene · 2016Article
- Nuclear β-arrestin1 is a critical cofactor of hypoxia-inducible factor-1α signaling in endothelin-1-induced ovarian tumor progression.Oncotarget · 2016Article
- Endothelin therapeutics in cancer: Where are we?American journal of physiology. Regulatory, integrative and comparative physiology · 2016Review
- Article
- The challenge of targeting metastasis.Cancer metastasis reviews · 2015Review
- The role of endothelin-1 and endothelin receptor antagonists in inflammatory response and sepsis.Archivum immunologiae et therapiae experimentalis · 2015Review
- Article
- Macitentan: first global approval.Drugs · 2014Article
- Endothelin-1 promotes survival and chemoresistance in chronic lymphocytic leukemia B cells through ETA receptor.PloS one · 2014Article
- Endothelin 1 in cancer: biological implications and therapeutic opportunities.Nature reviews. Cancer · 2013Review
- Endothelin receptor-A is required for the recruitment of antitumor T cells and modulates chemotherapy induction of cancer stem cells.Cancer biology & therapy · 2013Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Endothelin receptors (ETRs) are often overexpressed in ovarian tumors, which can be resistant to conventional therapies. Thus, we investigated whether blockage of the ETR pathways using the dual ETR antagonist macitentan combined with taxol or cisplatinum can produce therapy for orthotopically growing multidrug-resistant (MDR) human ovarian carcinoma. In several studies, nude mice were injected in the peritoneal cavity with HeyA8-MDR human ovarian cancer cells. Ten days later, mice were randomized to receive vehicle (saline), macitentan (oral, daily), taxol (intraperitoneal, weekly), cisplatinum (intraperitoneal, weekly), macitentan plus taxol, or macitentan plus cisplatinum. Moribund mice were killed, and tumors were collected, weighed, and prepared for immunohistochemical analysis. The HeyA8-MDR tumors did not respond to taxol, cisplatinum, or macitentan administered as single agents. In contrast, combination therapy with macitentan and taxol or macitentan and cisplatinum significantly decreased the tumor incidence and weight and significantly increased the survival of mice and their general condition. Multiple immunohistochemical analyses revealed that treatment with macitentan and macitentan plus taxol or cisplatinum inhibited the phosphorylation of ETRs, decreased the levels of pVEGFR2, pAkt, and pMAPK in tumor cells after 2 weeks of treatment and induced a first wave of apoptosis in tumor-associated endothelial cells followed by apoptosis in surrounding tumor cells. Our study shows that ovarian cancer cells, which express the endothelin axis and are multidrug resistant, are exquisitely sensitive to treatment with a dual ET antagonist and can be resensitized to both taxol and cisplatinum. This combined therapy led to a significant reduction in tumor weight.
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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.