Zebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discovery
Yin J, Zhao G, Kalirai H, Coupland SE, Jochemsen AG, Forn-Cuni G, Wierenga APA, Jager MJ, Snaar-Jagalska BE, Groenewoud A (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 16
Article Number: 598
Journal Issue: 4
DOI: 10.3390/ph16040598
Abstract
Uveal melanoma (UM) is a rare malignant cancer of the eye, with up to 50% of patients dying from metastasis, for which no effective treatment is available. Due to the rarity of the disease, there is a great need to harness the limited material available from primary tumors and metastases for advanced research and preclinical drug screening. We established a platform to isolate, preserve, and transiently recover viable tissues, followed by the generation of spheroid cultures derived from primary UM. All assessed tumor-derived samples formed spheroids in culture within 24 h and stained positive for melanocyte-specific markers, indicating the retention of their melanocytic origin. These short-lived spheroids were only maintained for the duration of the experiment (7 days) or re-established from frozen tumor tissue acquired from the same patient. Intravenous injection of fluorescently labeled UM cells derived from these spheroids into zebrafish yielded a reproducible metastatic phenotype and recapitulated molecular features of the disseminating UM. This approach allowed for the experimental replications required for reliable drug screening (at least 2 individual biological experiments, with n > 20). Drug treatments with navitoclax and everolimus validated the zebrafish patient-derived model as a versatile preclinical tool for screening anti-UM drugs and as a preclinical platform to predict personalized drug responses.
Additional Organisation(s)
Involved external institutions
Netherlands (NL)
United Kingdom (GB)How to cite
APA:
Yin, J., Zhao, G., Kalirai, H., Coupland, S.E., Jochemsen, A.G., Forn-Cuni, G.,... Groenewoud, A. (2023). Zebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discovery. Pharmaceuticals, 16(4). https://dx.doi.org/10.3390/ph16040598
MLA:
Yin, Jie, et al. "Zebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discovery." Pharmaceuticals 16.4 (2023).
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