Zebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discovery

dc.contributor.authorYin, Jie
dc.contributor.authorZhao, Gangyin
dc.contributor.authorKalirai, Helen
dc.contributor.authorCoupland, Sarah E.
dc.contributor.authorJochemsen, Aart G.
dc.contributor.authorForn-Cuní, Gabriel
dc.contributor.authorWierenga, Annemijn P. A.
dc.contributor.authorJager, Martine J.
dc.contributor.authorSnaar-Jagalska, B. Ewa
dc.contributor.authorGroenewoud, Arwin
dc.date.accessioned2023-05-11
dc.date.available2023-10-09T21:52:18Z
dc.date.created2023
dc.date.issued2023-05-11
dc.description.abstractUveal 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.en
dc.identifier.citationPharmaceuticals 16.4 (2023): 598. <https://www.mdpi.com/1424-8247/16/4/598>
dc.identifier.doihttps://doi.org/10.3390/ph16040598
dc.identifier.issn1424-8247
dc.identifier.opus-id22858
dc.identifier.urihttps://open.fau.de/handle/openfau/22858
dc.identifier.urnurn:nbn:de:bvb:29-opus4-228580
dc.language.isoen
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjecteye
dc.subjectoncology
dc.subjectuveal melanoma
dc.subjectxenograft
dc.subjectzebrafish
dc.subjectdrug toxicity
dc.subjectdrug screening
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleZebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discoveryen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.date.prevpublished2023-04-15
local.document.articlenumber598
local.journal.issue4
local.journal.titlePharmaceuticals
local.journal.volume16
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.importimport
local.subject.sammlungUniversität Erlangen-Nürnberg / Eingespielte Open Access Artikel / Eingespielte Open Access Artikel 2023
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