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Rhabdomyosarcoma xenotransplants in zebrafish embryos
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  • Jakob Siebert,
  • Michaela Schneider,
  • Daniela Reuter-Schmitt,
  • Julia Würtemberger,
  • Annette Neubüser,
  • Wolfgang Driever,
  • Simone Hettmer,
  • Friedrich Kapp
Jakob Siebert
Universitatsklinikum Freiburg

Corresponding Author:[email protected]

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Michaela Schneider
Universitatsklinikum Freiburg
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Daniela Reuter-Schmitt
Albert-Ludwigs-Universitat Freiburg Fakultat fur Biologie
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Julia Würtemberger
Universitatsklinikum Freiburg
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Annette Neubüser
Albert-Ludwigs-Universitat Freiburg Fakultat fur Biologie
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Wolfgang Driever
Albert-Ludwigs-Universitat Freiburg Fakultat fur Biologie
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Simone Hettmer
Universitatsklinikum Freiburg
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Friedrich Kapp
Universitatsklinikum Freiburg
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Abstract

Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. High-risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost-efficient estimates of anti-tumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish-based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water-soluble chemicals. Under optimized temperature conditions, embryonal RMS-xenografts were established in zebrafish embryos at 3 hours post fertilization (hpf). In proof-of-principle experiments, chemotherapy drugs with established clinical anti-RMS efficacy (vincristine, dactinomycin) and the MEK inhibitor trametinib were shown to significantly reduce the cross-sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost-effective solution for pre-clinical candidate drug testing.
13 Jun 2022Submitted to Pediatric Blood & Cancer
13 Jun 2022Submission Checks Completed
13 Jun 2022Assigned to Editor
19 Jun 2022Reviewer(s) Assigned
30 Jun 2022Review(s) Completed, Editorial Evaluation Pending
04 Jul 2022Editorial Decision: Revise Major
12 Sep 20221st Revision Received
12 Sep 2022Submission Checks Completed
12 Sep 2022Assigned to Editor
13 Sep 2022Reviewer(s) Assigned
15 Sep 2022Review(s) Completed, Editorial Evaluation Pending
21 Sep 2022Editorial Decision: Accept
Jan 2023Published in Pediatric Blood & Cancer volume 70 issue 1. 10.1002/pbc.30053