PUBLICATION
Zebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discovery
- Authors
- Yin, J., Zhao, G., Kalirai, H., Coupland, S.E., Jochemsen, A.G., Forn-Cuní, G., Wierenga, A.P.A., Jager, M.J., Snaar-Jagalska, B.E., Groenewoud, A.
- ID
- ZDB-PUB-230429-64
- Date
- 2023
- Source
- Pharmaceuticals (Basel, Switzerland) 16(4): (Journal)
- Registered Authors
- Snaar-Jagalska, Ewa B.
- Keywords
- drug screening, drug toxicity, eye, oncology, uveal melanoma, xenograft, zebrafish
- MeSH Terms
- none
- PubMed
- 37111355 Full text @ Pharmaceuticals (Basel)
Citation
Yin, J., Zhao, G., Kalirai, H., Coupland, S.E., Jochemsen, A.G., Forn-Cuní, G., Wierenga, A.P.A., Jager, M.J., Snaar-Jagalska, B.E., Groenewoud, A. (2023) Zebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discovery. Pharmaceuticals (Basel, Switzerland). 16(4):.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping