(164au) Integrating Metabolomics and Fluxomics to Study Cancer Metabolism in Low Glucose Environments

Metabolomics and fluxomics are integral tools for quantitative metabolic analysis. By combining mass spectrometry, isotope tracing, and mathematical modeling, we can quantify metabolite concentrations and fluxes in cancer cells. Using these tools, we investigated the coordination of bioenergetics, biosynthesis, and redox metabolism of cancer cells in the tumor microenvironment. We hypothesized that the tumor microenvironment plays a significant role in dictating cancer cell survival and proliferation. To shed light on how cancer cells use the tumor microenvironment, we assessed their adaptability to high levels of lactate. While cancer cells did not have a growth advantage over healthy cells in the high-lactate environment, we found that an intermittent supply of glucose allowed cancer cells to proliferate faster than healthy cells. By tracing stable isotopes from lactate and glutamine across metabolism, we elucidated the role of lactate in cancer cell survival via gluconeogenesis and energy metabolism.