Dual endothelin receptor inhibition enhances T-DM1 efficacy in brain metastases from HER2-positive breast cancer
| Autor: | Dai Fukumura, Gino B. Ferraro, David P. Kodack, Christina S. F. Wong, Vasileios Askoxylakis, Mark Badeaux, Isabelle Kirst, Dan G. Duda, Rakesh K. Jain, Ram C. Shankaraiah |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Brief Communication
lcsh:RC254-282 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Stroma HER2 Positive Breast Cancer Medicine Pharmacology (medical) Radiology Nuclear Medicine and imaging Cytotoxicity skin and connective tissue diseases 030304 developmental biology Macitentan 0303 health sciences business.industry medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Oncology chemistry 030220 oncology & carcinogenesis Cancer cell Cancer research Chemoprotective business Endothelin receptor |
| Zdroj: | NPJ Breast Cancer npj Breast Cancer, Vol 5, Iss 1, Pp 1-4 (2019) |
| ISSN: | 2374-4677 |
| Popis: | The effective treatment of cerebral metastases from HER2-positive breast cancer remains an unmet need. Recent studies indicate that activated astrocytes and brain endothelial cells exert chemoprotective effects on cancer cells through direct physical interaction. Here we report that the endothelin axis mediates protection of HER2-amplified brain metastatic breast cancers to the anti-HER2 antibody–drug conjugate ado-trastuzumab emtansine (T-DM1). Macitentan, a dual inhibitor of endothelin receptors A and B, improves the efficacy of T-DM1 against breast cancers grown in the brain. We show that direct contact of brain stroma with cancer cells is required for protection to T-DM1. Our data suggest that targeting the endothelin axis may be beneficial when anti-signaling agent and cytotoxic agent are combined. These findings may contribute to the development of therapeutic approaches with enhanced efficacy in the brain microenvironment. |
| Databáze: | OpenAIRE |
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