UC Berkeley

Cancer cells reprogram cellular metabolism to support growth and maintain pathogenicity. Since Otto Warburg’s discovery nearly a century ago that cancer cells have heightened glucose uptake and aerobic glycolysis, many studies have identified additional metabolic alterations required to maintain proliferation and cancer pathogenicity, such as heightened de novo lipogenesis and glutamine-dependent anaplerosis. These studies have provided a foundation for understanding the metabolic alterations that support tumorigenesis and cancer pathogenicity, but additional studies are required to uncover novel dysregulated metabolic pathways to fully understand the biochemical consequences of cancer.

In chapter one, we present several potential mechanisms that yield insight into the relationship between lipids and cancer. In chapter two, using an isotopic metabolomic platform, we elucidate the role of exogenous fatty acids in several types of cancer cells, putting forth an additional mechanism to describe the role of lipid metabolism in cancer. Although dysregulated lipid metabolism is a key feature of many cancers, the metabolic alterations in certain subtypes of cancer remain poorly understood. In chapter three, we use a reactivity-based chemoproteomic platform in combination with a metabolomic platform to identify GSTP1 as a novel metabolic enzyme target that is heightened in triple negative breast cancers (TNBCs), a highly malignant subtype of breast cancer that is poorly understood. Taken together, these studies highlight critical metabolic alterations in cancer to not only uncover novel metabolic pathways that drive cancer, but also lead to the development of novel therapeutic options for the treatment of cancer.