Metabolic adaptations of cancer in extreme tumor microenvironments

Cancer cells are highly heterogeneous to adapt to extreme tumor microenvironments (TMEs). TMEs 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 TME 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 TMEs is necessary, however, most are still elusive. Recently, adaptation of cancer cells within the TME 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 the potential as new cancer therapy targets, as they play essential roles in the metabolic adaptation of cancer cells to the TME. In this manuscript, we review (1) metabolic adaptations within tumor microenvironments through (2) cell-to-cell, and (3) organelle-organelle metabolic interactions.

Automated summary

Cancer cells are highly heterogeneous and adapt to harsh tumor microenvironments through genetic, epigenetic, and metabolic alterations. The metabolic adaptation allows cancer cells to evade death, immune responses, and develop drug resistance. Understanding metabolic adaptations of malignant cancer cells within tumor microenvironments is crucial for developing effective cancer therapies. Recent studies have shown that cell-cell and organelle-organelle interactions play essential roles in the metabolic adaptation of cancer cells, offering new targets for cancer treatment.