Mitochondria Deregulations in Cancer Offer Several Potential Targets of Therapeutic Interventions

Mitochondria play a key role in cancer and their involvement is not limited to the production of ATP only. Mitochondria also produce reactive oxygen species and building blocks to sustain rapid cell proliferation; thus, the deregulation of mitochondrial function is associated with cancer disease development and progression. In cancer cells, a metabolic reprogramming takes place through a different modulation of the mitochondrial metabolic pathways, including oxidative phosphorylation, fatty acid oxidation, the Krebs cycle, glutamine and heme metabolism. Alterations of mitochondrial homeostasis, in particular, of mitochondrial biogenesis, mitophagy, dynamics, redox balance, and protein homeostasis, were also observed in cancer cells. The use of drugs acting on mitochondrial destabilization may represent a promising therapeutic approach in tumors in which mitochondrial respiration is the predominant energy source. In this review, we summarize the main mitochondrial features and metabolic pathways altered in cancer cells, moreover, we present the best known drugs that, by acting on mitochondrial homeostasis and metabolic pathways, may induce mitochondrial alterations and cancer cell death. In addition, new strategies that induce mitochondrial damage, such as photodynamic, photothermal and chemodynamic therapies, and the development of nanoformulations that specifically target drugs in mitochondria are also described. Thus, mitochondria-targeted drugs may open new frontiers to a tailored and personalized cancer therapy.

Automated summary

Mitochondria play a crucial role in cancer, as they are involved in various metabolic pathways and their dysfunction is linked to cancer development. Alterations in mitochondrial homeostasis, including biogenesis, dynamics, and redox balance, have been observed in cancer cells. Drugs that target mitochondrial destabilization may offer a promising therapeutic approach for tumors that heavily rely on mitochondrial respiration. This review provides an overview of the mitochondrial features and metabolic pathways that are altered in cancer cells, as well as the potential drugs and strategies that induce mitochondrial damage for effective cancer therapy.