Annette Neubüser

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.