Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas

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dc.contributor.authorKlotz, Barbara
dc.contributor.authorKneitz, Susanne
dc.contributor.authorLu, Yuan
dc.contributor.authorBoswell, William T.
dc.contributor.authorPostlethwait, John
dc.contributor.authorWarren, Wesley C.
dc.contributor.authorWalter, Ronald B.
dc.contributor.authorSchartl, Manfred
dc.date.accessioned2019-07-30T17:48:28Z
dc.date.available2019-07-30T17:48:28Z
dc.date.issued2019-01
dc.description.abstractSmall aquarium fish models provide useful systems not only for a better understanding of the molecular basis of many human diseases, but also for first-line screening to identify new drug candidates. For testing new chemical substances, current strategies mostly rely on easy to perform and efficient embryonic screens. Cancer, however, is a disease that develops mainly during juvenile and adult stage. Long-term treatment and the challenge to monitor changes in tumor phenotype make testing of large chemical libraries in juvenile and adult animals cost prohibitive. We hypothesized that changes in the gene expression profile should occur early during anti-tumor treatment, and the disease-associated transcriptional change should provide a reliable readout that can be utilized to evaluate drug-induced effects. For the current study, we used a previously established medaka melanoma model. As proof of principle, we showed that exposure of melanoma developing fish to the drugs cisplatin or trametinib, known cancer therapies, for a period of seven days is sufficient to detect treatment-induced changes in gene expression. By examining whole body transcriptome responses we provide a novel route toward gene panels that recapitulate anti-tumor outcomes thus allowing a screening of thousands of drugs using a whole-body vertebrate model. Our results suggest that using disease-associated transcriptional change to screen therapeutic molecules in small fish model is viable and may be applied to pre-clinical research and development stages in new drug discovery.
dc.description.departmentChemistry and Biochemistry
dc.formatText
dc.format.extent10 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationKlotz, B., Kneitz, S., Lu, Y., Boswell, W., Postlethwait, J., Warren, W., Walter, R. B., & Schartl, M. (2019). Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas. G3: Genes, Genomes, Genetics, 9(7), pp. 2267-2276.
dc.identifier.doihttps://doi.org/10.1534/g3.119.400051
dc.identifier.urihttps://hdl.handle.net/10877/8419
dc.language.isoen
dc.publisherGenetics Society of America
dc.rights.holder© 2019 Klotz et al.
dc.rights.licenseThis work is licensed under a Creative Commons Attribution 4.0 International License.
dc.sourceG3: Genes, Genomes, Genetics, July 2019, Vol. 9, No. 7, pp. 2267-2276.
dc.subjecttransgenic Medaka Model
dc.subjectmelanoma
dc.subjectRNA-sequencing
dc.subjectanti-cancer drugs
dc.subjectgene expression signature
dc.subjectChemistry and Biochemistry
dc.titleExpression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas
dc.typeArticle

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