Graduation Year


Embargo Period


Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Igor Kuzin




Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. RMS rarely occurs in adults, but the outcome is significantly worse. Most adult patients with advanced RMS die because their cancer exhibits or develops resistance to available therapies. Chemotherapy treatment for RMS includes Doxorubicin, a DNA intercalating agent and topoisomerase II inhibitor, and Vincristine, a mitosis inhibitor. Histologically, RMS is classified into two main subtypes, embryonal (ERMS) and alveolar (ARMS). ARMS tumors typically harbor chromosomal translocations resulting in the expression of PAX3- or PAX7-FOXO1 fusion proteins. ERMS tumors exhibit a much wider range of genetic abnormalities. The fact that RMS of the same subtype may have significant difference in clinical behavior has been well recognized. Previously, we have shown that RMS cell lines propagated in vitro are heterogeneous with respect to expression of Myoblast determination protein 1 (MyoD1) and Noggin (Nog). Importantly, MyoD+/Nog+ cells have shown higher levels of chemoresistance to Vincristine and Doxorubicin than MyoD negative cells in part to upregulation of anti-apoptotic genes Gli-1 and BcL2 (Dawson et al 2020).



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