The influence of nutrient availability on tumor metabolism

Abstract

Tumor growth and progression are profoundly influenced by nutrient availability in the tumor microenvironment (TME). Nutrient accessibility not only shapes cancer metabolism but also affects therapeutic responses, genetic dependencies, and metastatic behavior. This dissertation explores how nutrient availability modulates these cancer phenotypes. First, we examined how environmental nutrient levels influence the efficacy of drugs targeting metabolic enzymes, showing that their effectiveness varies under different nutrient conditions. We also found that the nutrient composition of the TME in solid tumors is primarily determined by the tissue of origin rather than by the tumor itself. By contrast, leukemia cells actively reshape their nutrient environment. Furthermore, we assessed the impact of physiological nutrient conditions on genetic dependencies, identifying numerous genes whose essentiality is dictated by nutrient levels and uncovering potential new therapeutic targets in leukemia. Finally, we established that single nutrients do not dictate metastatic site preference. Instead, metastatic growth is driven by a complex interplay among multiple nutrients in the microenvironment and the intrinsic properties of cancer cells. These findings provide critical insights into how the nutrient environment influences tumor metabolism.