Targeting the metabolic enzyme DGAT1 to treat glioblastoma

INDICATION: Brain cancer

DGAT1 inhibition could treat glioblastoma multiforme (GBM) by promoting fat catabolism. Levels of triglycerides and lipid droplets were higher in postmortem brain tissue from GBM patients than individuals without cancer. Among patients with brain cancer, tumor levels of DGAT1 protein were higher in grade IV GBM than lower grades, and high DGAT1 protein levels in tumor tissue were associated with poor survival among grade IV patients. In human GBM cell lines, a tool compound DGAT1 inhibitor or an shRNA against DGAT1 reduced triglyceride levels and lipid droplet numbers and increased cell death. In two xenograft mouse models of GBM, tumor-specific DGAT1 knockdown or the DGAT1 inhibitor reduced tumor growth and lipid droplet formation, and extended survival. Next steps include mechanistic studies of DGAT1 in GBM...