UCLA

Alterations in lipid metabolism are a hallmark of cancer and provide potential for therapeutic exploitation in the universally lethal brain tumor glioblastoma (GBM). However, an understanding of how distinct molecular features impact lipid metabolism is required for the development of effective targeted therapies. Importantly, extrinsic factors within the tumor microenvironment shape lipid metabolism, necessitating investigation within physiologic contexts. In these studies, we have performed a comprehensive characterization of the GBM lipidome through the unbiased analysis of transcriptomic, genomic, and lipidomic datasets spanning diverse tumor microenvironments and encompassing the intertumoral molecular heterogeneity observed in GBM. In the first portion of this work, we discuss the many tumor intrinsic and extrinsic factors that lead to metabolic vulnerabilities in GBM. In the second portion of this work, we identify a novel regulator of the GBM lipidome and demonstrate the resulting metabolic vulnerabilities that occur as a result of this altered lipid metabolism.