Rhabdomyosarcoma xenotransplants in zebrafish embryos

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 antitumor efficacy of cand...

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Veröffentlicht in:Pediatric blood & cancer 2023-01, Vol.70 (1), p.e30053-n/a
Hauptverfasser: Siebert, Jakob, Schneider, Michaela, Reuter‐Schmitt, Daniela, Würtemberger, Julia, Neubüser, Annette, Driever, Wolfgang, Hettmer, Simone, Kapp, Friedrich G.
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container_issue 1
container_start_page e30053
container_title Pediatric blood & cancer
container_volume 70
creator Siebert, Jakob
Schneider, Michaela
Reuter‐Schmitt, Daniela
Würtemberger, Julia
Neubüser, Annette
Driever, Wolfgang
Hettmer, Simone
Kapp, Friedrich G.
description 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 antitumor 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 h postfertilization (hpf). In proof‐of‐principle experiments, chemotherapy drugs with established clinical anti‐RMS efficacy (vincristine, dactinomycin) and the mitogen‐activated protein kinase kinase 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 preclinical candidate drug testing.
doi_str_mv 10.1002/pbc.30053
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subjects Animals
Antitumor activity
Cell culture
Chemotherapy
Child
Dactinomycin
Danio rerio
Drug development
Drug screening
Embryos
Enzyme inhibitors
Hematology
Heterografts
Humans
Kinases
Mammals
Metastases
Oncology
Pediatrics
Precision medicine
Protein kinase
Rhabdomyosarcoma
Rhabdomyosarcoma - drug therapy
Rhabdomyosarcoma - pathology
Rhabdomyosarcoma, Embryonal - drug therapy
RMS
Tumor cells
Vincristine
xenograft
Xenograft Model Antitumor Assays
Xenografts
Zebrafish
zebrafish embryo
title Rhabdomyosarcoma xenotransplants in zebrafish embryos
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