Rhabdomyosarcoma xenotransplants in zebrafish embryos.
Pediatr Blood Cancer
; 70(1): e30053, 2023 01.
Article
in En
| MEDLINE
| ID: mdl-36317680
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 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rhabdomyosarcoma
/
Rhabdomyosarcoma, Embryonal
Limits:
Animals
/
Child
/
Humans
Language:
En
Journal:
Pediatr Blood Cancer
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Year:
2023
Type:
Article
Affiliation country:
Germany