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Title:Determining the Mechanism of 5-aza Hypersensitivity in Testicular Germ Cell Tumors
Author(s):Khan, Ema M; Rodriguez, Jennifer C.; Bikorimana, Emmanuel
Contributor(s):Spinella, Michael
Subject(s):Testicular Germ Cell Tumor
Interferon Pathway
Comparative Biosciences
Abstract:Testicular germ cell tumors (TGCT) are the most common type of cancer in young men. Patients are successfully treated with a combination of cisplatin, bleomycin, and etoposide. However, 15-20% of patients are refractory to cisplatin treatment or undergo late relapse. We have previously shown that these refractory TGCT cells are highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). However, the mechanism is unknown. Recent studies suggest that 5-aza targets certain types of cancer cells, like colorectal and ovarian, by inducing the viral mimicry pathway. We hypothesize the mechanism of 5-aza hypersensitivity in TGCT cells is due to hyperactivation of immune surveillance pathways including the endogenous retroviral (ERV) dsRNA MDA5/MAVS/IRF7 pathway. We demonstrate that interferon stimulated genes are induced with 5-aza treatment in TGCT cell lines. However, silencing MAVS and TLR3 of the viral mimicry pathway did not inhibit the antitumor effects of 5-aza. The results demonstrate that 5-aza hypersensitivity in TGCT is not due to hyperactivation of immune surveillance pathways, but the pathway may be necessary for the survival of TGCT cells. For future studies, we will explore the use of 5-aza treatment and the blockage of the viral mimicry pathway as a treatment of TGCT.
Issue Date:2018-04
Genre:Conference Poster
Rights Information:Copyright 2018 Jennifer C. Rodriguez
Copyright 2018 Ema Khan
Copyright 2018 Emmanuel Bikorimana
Date Available in IDEALS:2018-05-03

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