Rational combination treatment targets different aspects of PAX3/FKHR oncogenicity

PAX3/FKHR is an oncogenic transcription factor that acts through transcriptional deregulation of target genes, either by activation or repression. We have shown previously that the transcriptional activity of PAX3/FKHR on target genes such as AP2beta or CB1 depends on specific phosphorylation in a peptide located between the two DNA-binding domains. This activity can be targeted by multi-kinase inhibitors such as PKC412 both in vitro as well as in vivo. Here, we demonstrate that PAX3/FKHR mediates repression of p21Cip1 and that downregulation of p21 contributes to survival of aRMS cells. This repression is media…