Metabolic Adaptations of Cancer in Extreme Tumor Microenvironments.

Cancer cells are highly heterogeneous in order to adapt to extreme tumor microenvironments. Tumor microenvironments challenge cancer cells via hypoxia, nutrition starvation, and acidic pH, promoting invasion and metastasis concomitant with genetic, epigenetic, and metabolic alterations. Metabolic adaptation to an extreme tumor microenvironment could allow cancer cells to evade cell death and immune responses, as well as resulting in drug resistance, recurrence and poor patient prognosis. Therefore, elucidation of the metabolic adaptation of malignant cancer cells within tumor microenvironments is necessary, however, most are still elusive. Recently, adaptation of cancer cells within the tumor microenvironment can be analyzed via cell-cell interactions at the single cell level. In addition, information into organelle-organelle interactions has recently been obtained. These cell-cell, and organelle-organelle interactions demonstrate potential as new cancer therapy targets, as they play essential roles in the metabolic adaptation of cancer cells to the tumor microenvironment. In this manuscript, we review (1) metabolic adaptations within tumor microenvironments through (2) cell-to-cell, and (3) organelle-organelle metabolic interactions.