Mitochondrial Ca²⁺ in Cancer Growth and Metabolism

Cancer is a leading cause of death in developed countries, despite many breakthroughs in targeted small molecule and immunotherapeutic interventions. A deeper understanding of the characteristics and processes that underlie malignancy will enable us to develop more effective therapeutic options to improve patient outcomes. One particular area of interest is in cancer cell metabolism. Even as early as the 1920s, Otto Warburg recognized dysregulated metabolism in cancerous cells. Altered metabolism may provide targetable nutrient dependencies for further clinical development, either by nutrient restriction or pathway inhibition. More recently, researchers have observed an increasingly strong linkage between altered mitochondrial Ca²⁺ homeostasis and tumor cell metabolism, with strong implications for therapeutic targeting. In this review, we summarize the literature surrounding mitochondrial Ca²⁺ homeostasis, metabolism, and cancer, as well as providing a discussion of the potential for mitochondrial Ca²⁺ modulation as an anticancer therapeutic modality.