دورية أكاديمية
Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure
| العنوان: | Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure |
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| المؤلفون: | Smith, Michael P, Rowling, Emily J, Miskolczi, Zsofia, Ferguson, Jennifer, Spoerri, Loredana, Haass, Nikolas K, Sloss, Olivia, McEntegart, Sophie, Arozarena, Imanol, von Kriegsheim, Alex, Rodriguez, Javier, Brunton, Holly, Kmarashev, Jivko, Levesque, Mitchell P, Dummer, Reinhard, Frederick, Dennie T, Andrews, Miles C, Cooper, Zachary A, Flaherty, Keith T, Wargo, Jennifer A, Wellbrock, Claudia |
| المصدر: | Smith, Michael P; Rowling, Emily J; Miskolczi, Zsofia; Ferguson, Jennifer; Spoerri, Loredana; Haass, Nikolas K; Sloss, Olivia; McEntegart, Sophie; Arozarena, Imanol; von Kriegsheim, Alex; Rodriguez, Javier; Brunton, Holly; Kmarashev, Jivko; Levesque, Mitchell P; Dummer, Reinhard; Frederick, Dennie T; Andrews, Miles C; Cooper, Zachary A; Flaherty, Keith T; Wargo, Jennifer A; Wellbrock, Claudia (2017). Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure. EMBO Molecular Medicine, 9(8):1011-1029. |
| بيانات النشر: | Wiley Open Access |
| سنة النشر: | 2017 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Dermatology Clinic, 610 Medicine & health |
| الوصف: | Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a "MITF-high" phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance "AXL-high" phenotype. > 50% of melanomas progress with enriched "AXL-high" populations, and because AXL is linked to de-differentiation and invasiveness avoiding an "AXL-high relapse" is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF-induced expression of endothelin 1 (EDN1). EDN1 expression is enhanced in tumours of patients on treatment and confers drug resistance through ERK re-activation in a paracrine manner. Most importantly, EDN1 not only supports MITF-high populations through the endothelin receptor B (EDNRB), but also AXL-high populations through EDNRA, making it a master regulator of phenotype heterogeneity. Endothelin receptor antagonists suppress AXL-high-expressing cells and sensitize to BRAF inhibition, suggesting that targeting EDN1 signalling could improve BRAF inhibitor responses without selecting for AXL-high cells. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1757-4676 |
| العلاقة: | https://www.zora.uzh.ch/id/eprint/139241/1/706_Smith_MP._et_al._Targeting_endothelin_receptor_signalling_overcomes_heterogeneity_driven_therapy_failure_EMBO_Mol_Med._2017.pdfTest; info:pmid/28606996; urn:issn:1757-4676 |
| DOI: | 10.5167/uzh-139241 |
| DOI: | 10.15252/emmm.201607156 |
| الإتاحة: | https://doi.org/10.5167/uzh-13924110.15252/emmm.201607156Test https://www.zora.uzh.ch/id/eprint/139241Test/ https://www.zora.uzh.ch/id/eprint/139241/1/706_Smith_MP._et_al._Targeting_endothelin_receptor_signalling_overcomes_heterogeneity_driven_therapy_failure_EMBO_Mol_Med._2017.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.D09EA0B2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17574676 |
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| DOI: | 10.5167/uzh-139241 |