Kephart (2015) Clin Can Research (Link to abstract)
In this study, negative regulators of the Wnt pathway were found to be upregulated in an expression array of myoblasts expressing the PAX3-FOXO1 fusion transcript. In particular, a gene called SFRP3 was upregulated and appears to play a key role. In several functional tests this protein was confirmed to be important both for proliferation of alveolar rhabdomyosarcoma (aRMS) cells and for downregulation of the Wnt pathway within those cells. An aRMS xenograft with a suppressible SFRP3 overexpression was established in mice. 5/7 of these mice showed no detectable tumor at necropsy when SFRP3 was suppressed and treatment with vincristine was also given.
*This study establishes the Wnt pathway and upreguation of SFRP3 in particular as a potential key process in translocation positive aRMS. This may open the door for a targeted treatment in this difficult disease.