LAUSR

Atypical teratoid rhabdoid tumors (AT/RT) are deadly infantile brain tumors in dire need of new, targeted therapies. Recent molecular analysis revealed considerable tumor heterogeneity subdividing AT/RT into 3 distinct groups. The MYC subgroup has a dismal 5 year survival of 18.5%. MYC is known to drive reliance on glutamine for cellular metabolism suggesting that high-MYC expressing neoplasms may be sensitive to glutamine metabolic inhibitors. 6-Diazo-5-oxo-L-norleucine (DON) is a glutamine antagonist that decreases the tumorigenicity of high MYC expressing models of medulloblastoma and neuroblastoma . We hypothesize that DON will reduce the tumorigenicity of the MYC subgroup of AT/RT. High levels of c-MYC protein are expressed in about 1/3 of human AT/RT (Immunohistochemistry for c-MYC on 22 human AT/RT, H-score > 1 standard deviation over the median considered high c-MYC expression). Similarly two of six of AT/RT cell lines expressed high levels of c-MYC protein by western blot. DON treatment slowed cell growth of high c-MYC expressing AT/RT cell lines BT12 and CHLA06 (MTS assay p Citation Format: Sabrina Wang, Jeffrey Rubens, Sariah Allen, Brent Orr, Charles Eberhart, Eric Raabe. Targeting abnormal metabolism downstream of MYC in atypical teratoid/rhabdoid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5182. doi:10.1158/1538-7445.AM2017-5182