Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas
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...
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Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.119.400051 |
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doaj-36d68abce2a94c45b9196339619649222021-07-02T07:19:00ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362019-07-01972267227610.1534/g3.119.40005120Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka MelanomasBarbara KlotzSusanne KneitzYuan LuWilliam BoswellJohn PostlethwaitWesley WarrenRonald B. WalterManfred SchartlSmall 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.http://g3journal.org/lookup/doi/10.1534/g3.119.400051Gene expression signaturetransgenic medaka modelmelanomaRNA-sequencinganti-cancer drugs |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Barbara Klotz Susanne Kneitz Yuan Lu William Boswell John Postlethwait Wesley Warren Ronald B. Walter Manfred Schartl |
spellingShingle |
Barbara Klotz Susanne Kneitz Yuan Lu William Boswell John Postlethwait Wesley Warren Ronald B. Walter Manfred Schartl Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas G3: Genes, Genomes, Genetics Gene expression signature transgenic medaka model melanoma RNA-sequencing anti-cancer drugs |
author_facet |
Barbara Klotz Susanne Kneitz Yuan Lu William Boswell John Postlethwait Wesley Warren Ronald B. Walter Manfred Schartl |
author_sort |
Barbara Klotz |
title |
Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas |
title_short |
Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas |
title_full |
Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas |
title_fullStr |
Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas |
title_full_unstemmed |
Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas |
title_sort |
expression signatures of cisplatin- and trametinib-treated early-stage medaka melanomas |
publisher |
Oxford University Press |
series |
G3: Genes, Genomes, Genetics |
issn |
2160-1836 |
publishDate |
2019-07-01 |
description |
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. |
topic |
Gene expression signature transgenic medaka model melanoma RNA-sequencing anti-cancer drugs |
url |
http://g3journal.org/lookup/doi/10.1534/g3.119.400051 |
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