ArticleCell death & disease2023
Targeting tumor-stroma communication by blocking endothelin-1 receptors sensitizes high-grade serous ovarian cancer to PARP inhibition.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Predictive Value of PreoperativeInternational journal of molecular sciences · 2026Article
- EDNRA Forms a Positive Feedback Loop with the Hippo/YAP Axis to Drive Triple-Negative Breast Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Challenges and advances in drug resistance and tolerance in cancer.Journal of experimental & clinical cancer research : CR · 2026Review
- Nuclear gasdermin E drives endothelin-1-induced metastatic progression independently of the pyroptosis.Cell death & disease · 2026Article
- Advances in ovarian cancer: biological insights, therapeutic innovations, and future perspectives.Journal of ovarian research · 2025Review
- DNA damaging agents boost the transcription of endothelin A receptor in high-grade serous ovarian cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- The extracellular matrix protein type I collagen and fibronectin are regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts.Journal of experimental & clinical cancer research : CR · 2025Article
- Endothelin-1 as a Candidate Biomarker of Systemic Sclerosis: A GRADE-Assessed Systematic Review and Meta-Analysis With Meta-Regression.Biomarker insights · 2025Article
- Cancer Organoids as reliable disease models to drive clinical development of novel therapies.Journal of experimental & clinical cancer research : CR · 2024Article
- YAP signaling orchestrates the endothelin-1-guided invadopodia formation in high-grade serous ovarian cancer.Bioscience reports · 2024Article
- Endothelin-1 receptor blockade impairs invasion patterns in engineered 3D high-grade serous ovarian cancer tumouroids.Clinical science (London, England : 1979) · 2024Article
- The endothelin-1-driven tumor-stroma feed-forward loops in high-grade serous ovarian cancer.Clinical science (London, England : 1979) · 2024Article
- Endothelin and the tumor microenvironment: a finger in every pie.Clinical science (London, England : 1979) · 2024Review
- The β-arrestin1/endothelin axis bolsters ovarian fibroblast-dependent invadosome activity and cancer cell metastatic potential.Cell death & disease · 2024Article
- Endothelin-1 and Its Role in Cancer and Potential Therapeutic Opportunities.Biomedicines · 2024Review
- Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy.Aging cell · 2024Article
- Endothelin receptor antagonists (ERAs) can potentially be used as therapeutic drugs to reduce hypertension caused by small molecule tyrosine kinase inhibitors (TKIs).Frontiers in pharmacology · 2024Review
- The functionality of a therapeutic antibody candidate restored by a single mutation from proline to threonine in the variable region.Human vaccines & immunotherapeutics · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PARP inhibitors (PARPi) have changed the treatment paradigm of high-grade serous ovarian cancer (HG-SOC). However, the impact of this class of inhibitors in HG-SOC patients with a high rate of TP53 mutations is limited, highlighting the need to develop combinatorial therapeutic strategies to improve responses to PARPi. Here, we unveil how the endothelin-1/ET-1 receptor (ET-1/ET-1R) axis, which is overexpressed in human HG-SOC and associated with poor prognosis, instructs HG-SOC/tumor microenvironment (TME) communication via key pro-malignant factors and restricts the DNA damage response induced by the PARPi olaparib. Mechanistically, the ET-1 axis promotes the p53/YAP/hypoxia inducible factor-1α (HIF-1α) transcription hub connecting HG-SOC cells, endothelial cells and activated fibroblasts, hence fueling persistent DNA damage signal escape. The ET-1R antagonist macitentan, which dismantles the ET-1R-mediated p53/YAP/HIF-1α network, interferes with HG-SOC/stroma interactions that blunt PARPi efficacy. Pharmacological ET-1R inhibition by macitentan in orthotopic HG-SOC patient-derived xenografts synergizes with olaparib to suppress metastatic progression, enhancing PARPi survival benefit. These findings reveal ET-1R as a mechanistic determinant in the regulation of HG-SOC/TME crosstalk and DNA damage response, indicating the use of macitentan in combinatorial treatments with PARPi as a promising and emerging therapy.
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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.