ArticleNeoplasia (New York, N.Y.)2011
Macitentan (ACT-064992), a tissue-targeting endothelin receptor antagonist, enhances therapeutic efficacy of paclitaxel by modulating survival pathways in orthotopic models of metastatic human ovarian cancer.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Bicaudal‑C1 in Cancer: Molecular Mechanisms and Therapeutic Strategies Integrating Chinese and Western Medicine.Drug design, development and therapy · 2026Review
- Targeting the Endothelin-1 pathway to reduce invasion and chemoresistance in gallbladder cancer cells.Cancer cell international · 2023Article
- 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
- Targeting the endothelin axis as a therapeutic strategy for oral cancer metastasis and pain.Scientific reports · 2020Article
- Targeting endothelin 1 receptor-miR-200b/c-ZEB1 circuitry blunts metastatic progression in ovarian cancer.Communications biology · 2020Article
- Endothelin Receptor Antagonists: Status Quo and Future Perspectives for Targeted Therapy.Journal of clinical medicine · 2020Review
- 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
- Article
- Blocking endothelin-1-receptor/β-catenin circuit sensitizes to chemotherapy in colorectal cancer.Cell death and differentiation · 2017Article
- Targeting acid sphingomyelinase with anti-angiogenic chemotherapy.Cellular signalling · 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
- Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel.Neuro-oncology · 2016Article
- Article
- The role of endothelin-1 and endothelin receptor antagonists in inflammatory response and sepsis.Archivum immunologiae et therapiae experimentalis · 2015Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Potential treatments for ovarian cancers that have become resistant to standard chemotherapies include modulators of tumor cell survival, such as endothelin receptor (ETR) antagonist. We investigated the therapeutic efficacy of the dual ETR antagonist, macitentan, on human ovarian cancer cells, SKOV3ip1 and IGROV1, growing orthotopically in nude mice. Mice with established disease were treated with vehicle (control), paclitaxel (weekly, intraperitoneal injections), macitentan (daily oral administrations), or a combination of paclitaxel and macitentan. Treatment with paclitaxel decreased tumor weight and volume of ascites. Combination therapy with macitentan and paclitaxel reduced tumor incidence and further reduced tumor weight and volume of ascites when compared with paclitaxel alone. Macitentan alone occasionally reduced tumor weight but alone had no effect on tumor incidence or ascites. Immunohistochemical analyses revealed that treatment with macitentan and macitentan plus paclitaxel inhibited the phosphorylation of ETRs and suppressed the survival pathways of tumor cells by decreasing the levels of pVEGFR2, pAkt, and pMAPK. The dose of macitentan necessary for inhibition of phosphorylation correlated with the dose required to increase antitumor efficacy of paclitaxel. Treatment with macitentan enhanced the cytotoxicity mediated by paclitaxel as measured by the degree of apoptosis in tumor cells and tumor-associated endothelial cells. Collectively, these results show that administration of macitentan in combination with paclitaxel prevents the progression of ovarian cancer in the peritoneal cavity of nude mice in part by inhibiting survival pathways of both tumor cells and tumor-associated endothelial cells.
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