TMET-23. GLIOBLASTOMA EXHIBIT SEX DIFFERENCES IN BRANCHED-CHAIN AMINO ACID METABOLISM

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. It more prevalent males female patients exhibit a survival advantage. Understanding molecular mechanisms that underlie those sex differences could support novel treatment strategies. Amino acids, such as glutamine branched-chain amino acids (leucine, isoleucine, valine; BCAAs), play important roles GBM they are involved biosynthesis, energetics, redox homeostasis, mTOR signaling. Using murine transformed astrocytes, we recently discovered male cells dependent on utilize to replenish biosynthetic pathways, including BCAA regeneration. regeneration (i.e., re-amination of ketoacids BCAA) catalyzed by aminotransferases (BCATs) requires glutamate nitrogen donor. Importantly, has been linked cancer progression poor outcome. stable isotope labeling found astrocytes greater transfer from onto regenerate BCAAs. In line with increased utilization for via BCAT, BCAT1 protein expression levels. Concordantly, sensitive deprivation compared cells, indicating metabolism may sex-specific role GBM. human surgical specimens, metabolite abundance our findings dependency previous reports show differ between females under normal physiological conditions. Together, these data suggest BCAAs unique metabolism. Our highlight differs underline importance considering metabolic targeting approaches.