Famine versus feast: understanding the metabolism of tumors in vivo

•Quiescent metabolism is catabolic whereas proliferative metabolism requires anabolism.•Metabolic phenotypes in cell culture reflect proliferative metabolism.•Most cancer cells in vivo are not proliferating rapidly and may display distinct metabolism.•The in vivo context of a tumor cell, including hypoperfusion, can strongly influence metabolism.•Metabolic cooperation can exist among different cells within a tumor.

To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo.