ETMM-04. AURKA INHIBITION REPROGRAMS METABOLISM AND IS SYNTHETICALLY LETHAL WITH FATTY ACID OXIDATION INHIBITION IN GLIOBLASTOMA MODEL SYSTEMS

Cancer and inhibition of fatty acid oxidation

Recently, a “metabolic transformation” property with increased glycolytic rates (Warburg effect) was described for cancer cells. It has been shown that there is an active interaction between mutations of crucial enzymes involved in metabolic pathways and of oncogenes, whose effector proteins also exert metabolic functions. Interestingly, because many of these metabolic changes are confined to t...

ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency.

The DNA damage response kinase ATR and its effector kinase CHEK1 are required for cancer cells to survive oncogene-induced replication stress. ATR inhibitors exhibit synthetic lethal interactions, with deficiencies in the DNA damage response enzymes ATM and XRCC1 and with overexpression of the cell cycle kinase cyclin E. Here, we report a systematic screen to identify synthetic lethal interacti...

AURKA inhibition mimics BRCAness

Inhibition of the Polyamine Synthesis Pathway Is Synthetically Lethal with Loss of Argininosuccinate Synthase 1

Argininosuccinate synthase 1 (ASS1) is the rate-limiting enzyme for arginine biosynthesis. ASS1 expression is lost in a range of tumor types, including 50% of malignant pleural mesotheliomas. Starving ASS1-deficient cells of arginine with arginine blockers such as ADI-PEG20 can induce selective lethality and has shown great promise in the clinical setting. We have generated a model of ADI-PEG20...

Drug-Induced Inhibition of Mitochondrial Fatty Acid Oxidation and Steatosis

Word count (including the Abstract): 3843 Keywords: Amiodarone Drug Drug-induced liver disease Fatty acid oxidation Fatty liver Membrane potential Mitochondria Nucleoside reverse transcriptase inhibitors Obesity Oxidative phosphorylation Oxidative stress Reactive oxygen species Respiratory chain Steatosis Tamoxifen Tetracycline Triglycerides Valproic acid Abstract Drug-induced inhibition of mit...