Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas
Date
2019-01
Authors
Klotz, Barbara
Kneitz, Susanne
Lu, Yuan
Boswell, William T.
Postlethwait, John
Warren, Wesley C.
Walter, Ronald B.
Schartl, Manfred
Journal Title
Journal ISSN
Volume Title
Publisher
Genetics Society of America
Abstract
Small 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.
Description
Keywords
transgenic Medaka Model, melanoma, RNA-sequencing, anti-cancer drugs, gene expression signature, Chemistry and Biochemistry
Citation
Klotz, 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.
Rights
Rights Holder
© 2019 Klotz et al.
Rights License
This work is licensed under a Creative Commons Attribution 4.0 International License.