Introduction
Representing approximately 6% of all pediatric malignancies, soft
tissue sarcomas constitute the third most frequent extracranial solid
malignant tumor entity in children . Rhabdomyosarcomas (RMS) are the
most common pediatric soft tissue sarcomas and a heterogeneous group of
cancers. The main subgroups of RMS in children and adolescents are
alveolar and embryonal, which differ in their histology and genetic
underpinnings, but also their clinical behavior. Approximately 80% of
alveolar RMS (ARMS) are associated with the chromosomal translocations
t(2;13)(q35;q14) or t(1;13)(p36;q14) . These translocations lead to
fusions of the FOXO1 gene on chromosome 13 to the PAX3gene on chromosome 2 or the PAX7 gene on chromosome 1. The
resulting fusion genes PAX3-FOXO1 and PAX7- FOXO1 are
considered drivers of malignancy in ARMS . Embryonal RMS (ERMS) show a
higher degree of genetic diversity, including frequent RAS pathway gene
mutations and genetic imbalances such as loss of heterozygosity (LOH) at
chromosome locus 11p15 . This genomic region contains several genes that
play important roles in growth control and are therefore associated with
different types of embryonal tumors . There are major differences in
clinical characteristics, response to therapy and outcomes between
embryonal and alveolar RMS. The 5-year overall survival rate of
pediatric patients with RMS is approximately 70% . ARMS are generally
associated with substantially worse outcomes than ERMS . There is an
urgent need to establish the anti-RMS efficacy of candidate drugs and
improve long-term survival, especially for patients with relapsed or
metastatic disease, for whom survival rates continue to be dismal . In
this study, we sought to establish a rapid RMS research platform in
zebrafish embryos by implanting 3 hours-old zebrafish embryos with RMS
cells. RMS xenografts were shown to shrink in response to exposure to
anti-RMS drugs in proof-of-principle experiments.