The Tangled Mitochondrial Metabolism in Cancer: An Innovative Pharmacological Approach

Background: Mitochondria are remarkably gaining significant and different pathogenic roles in cancer (i.e., to sustain specific metabolism, to activate signaling pathways, to promote apoptosis resistance, to favor cancer cell dissemination, and finally to facilitate genome instability). Interestingly, all these roles seem to be linked to the fundamental activity of mitochondria, i.e. oxidative metabolism. Intriguingly, a typical modification of mitochondrial oxidative metabolism and reactive oxygen species production/ neutralization seems to have a central role in all these tangled pathogenic roles in cancer. On these bases, a careful understanding of the molecular relationships between cancer and mitochondria may represent a fundamental step to realize therapeutic approaches blocking the typical cancer progression. The main aim of this review is to stress some neglected aspects of oxidative mitochondrial metabolism of cancer cells to promote more translational research with diagnostic and therapeutic potential. Methods: We reviewed the available literature regarding clinical and experimental studies on various roles of mitochondria in cancer, with attention to the cancer cell mitochondrial metabolism. Results: Mitochondria are an important source of reactive oxygen species. Their toxic effects seem to increase in cancer cells. However, it is not clear if damage depends on ROS overproduction and/or defect in detoxification. Failure of both these processes is likely a critical component of the cancer process and is strictly related to the actual microenvironment of cancer cells. Conclusions: Mitochondria, also by ROS production, have a fundamental pathogenetic role in promoting and maintaining cancer and its spreading. To carefully understand the tangled redox state of cancer cells mitochondria represents a fundamental step to realize therapeutic approaches blocking the typical cancer progression.