Cell-intrinsic mechanisms of nutrient sensing are intimately linked to adaptive metabolic responses, and these pathways play critical roles in the complex and dynamic nutrient environment of a growing tumor. Nutrient-responsive transcription factors (e.g., HIF, SREBP, ATF4) and signaling pathways (e.g., mTORC1, AMPK) allow tumor cells to tune their metabolic output and strategies to fluctuations in nutrient availability, thus balancing tumor cell proliferation and survival with a combination of anabolic and adaptive responses. Coupling these nutrient-sensing mechanisms to the control of recycling and scavenging processes, such as autophagy and macropinocytosis, further enhances the adaptability to nutrients within tumors. Here, we discuss the key nutrient-sensing pathways active in cancer cells, how oncogenic events influence these pathways, and their likely contributions to tumor growth and survival. A better understanding of nutrient-sensing strategies and metabolic adaptations within the tumor microenvironment is critical to defining and targeting metabolic vulnerabilities in cancer.


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