Frontiers in Clinical Drug Research - Anti-Cancer Agents

Volume: 8

Towards Targeted Therapy: Anticancer Agents Targeting Cell Organelle Mitochondria

Author(s): Meghana Manjunath and Bibha Choudhary *

Pp: 218-282 (65)

DOI: 10.2174/9781681089317121080008

* (Excluding Mailing and Handling)

Abstract

Mitochondria are the key source of energy in cells. In a cancer cell, mitochondrial metabolism is deregulated to compensate for the energy requirements of the dividing cells. Mitochondria play a significant role in apoptosis by releasing the pro-apoptotic factors, which are also altered in cancer cells. In this context, the role of mitochondrial bioenergetics in regulating cancer stem cells, chemoresistance, and malignant transformation is just beginning to be unraveled. Additionally, mutations in mitochondrial enzymes can result in oncometabolite production, which acts as signal transducers that help in tumour growth. Mitochondria also play an important role in immune system evasion by altering the tumour microenvironment. All these make mitochondria a key target for cancer therapy. The mitochondrial outer membrane protein BCL2 is an anti-apoptotic protein against which a small-molecule inhibitor, Venetoclax, has been approved to treat leukaemia. Arsenic trioxide, a small-molecule inhibitor that targets complex IV in the inner membrane, has been approved by the US FDA to treat acute promyelocytic leukaemia. Metformin, a complex I inhibitor of the electron-transport chain, has shown a better effect on cancers having a mutation in complex I genes. Several drugs that can modulate the mitochondrial dynamics and functions are being tested for their anticancer property. This chapter discusses the mitochondrial functions in normal cells versus those in cancer cells and cancer stem cells. Anticancer therapy targeting mitochondrial proteins and processes is also elaborated. A catalogue of known mitochondrial mutations involved in cancer is presented. Immunotherapy using mutated mitochondrial proteins or peptides and immunometabolism as a target for cancer therapy is also discussed.


Keywords: BCL2, Cancer stem cells, Genome, Membrane, Metabolism, Mitochondria, Mutations, Therapy, Transcriptome.

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