Mitochondria-Targeting Therapeutic Strategies for Overcoming Chemoresistance and Progression of Cancer

Takashi      Morisaki; Mitsuo      Katano

Abstract

The cytotoxic effects of many anticancer drugs are mediated via the apoptotic pathways. Chemoresistant tumor cells have acquired the ability to evade the action of multiple classes of anti-cancer drugs. One mechanism by which tumor cells survive in the presence of chemotherapy is by increasing antiapoptotic activities. Since mitochondria are critical gatekeepers to the apoptosis process, development of cytotoxic drugs that target mitochondria may provide a new strategy to induce apoptosis in tumor cells. Mitochondrial permeability transition pore complex (PTPC) controls mitochondrial membrane permeabilization, which is a critical event in the process leading to chemotherapy-induced apoptosis. Therefore, targeting of PTPC components may overcome chemoresistance in tumor cells. Moreover, alterations in mitochondrial DNA such as mutation and the subsequent dysfunction of mitochondrial respiratory enzyme have been reported in various types of cancer, and their functional consequences are associated cancer development, chemoresistance, and therapeutic implications. In this mini-review, we aim to provide a brief review on several mitochondria-targeting strategies to overcome chemoresistance in cancer.

Keywords: mitochondria-targeting, chemoresistance, anticancer drugs, apoptosis, permeability transition pore complex, mitochondrial membrane permeabilization, mitochondria-targeting strategies

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