Identification of FDA approved drugs with anti-tumor activity in rhabdomyosarcoma.

This project will uncover genetic pathways and FDA approved drugs that have novel anti-tumor activity in a rare, pediatric malignancy of muscle -- embryonal rhabdomyosarcoma (ERMS).  Rhabdomyosarcoma effects over 250 patients annually in the United States, of which ERMS is the most common subtype.   Our work has already identified a key genetic pathway involved in ERMS tumor growth, the RAS pathway.  Remarkably, this same pathway is also perturbed in over 30% of all human cancer, suggesting that uncovering effective drugs for the treatment of ERMS may have more far reaching clinical implications for cancer as a whole.  We have identified a novel cell type in ERMS that is responsible for remaking tumor -- the ERMS cancer stem cell.  If one could selectively target these cells for destruction, tumor growth would likely be halted. Finally, we have identified 28 FDA-approved drugs with possible anti-tumor activity.  This is not surprising given that many of these drugs received FDA approval based on efficacy in treating non-cancerous diseases in humans. These chemicals will be assessed for the ability to curb tumor growth in a zebrafish model of ERMS and in human cell lines.   Moreover, we will assess if perturbation of RAS pathway components by these FDA approved drugs act by killing the cancer stem cell in ERMS.

Publication: Cancer Cell 21, 680–693, May 15, 2012. "In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma"