Classification of mitocans, anti-cancer drugs acting on mitochondria

Abstract

Mitochondria have emerged as an intriguing target for anti-cancer drugs, inherent to vast majority if not all types of tumours. Drugs that target mitochondria and exert anti-cancer activity have become a focus of recent research due to their great clinical potential (which has not been harnessed thus far). The exceptional potential of mitochondria as a target for anti-cancer agents has been reinforced by the discouraging finding that even tumours of the same type from individual patients differ in a number of mutations. This is consistent with the idea of personalised therapy, an elusive goal at this stage, in line with the notion that tumours are unlikely to be treated by agents that target only a single gene or a single pathway. This endows mitochondria, an invariant target present in all tumours, with an exceptional momentum. This train of thoughts inspired us to define a class of anti-cancer drugs acting by way of mitochondrial 'destabilisation', termed 'mitocans'. In this communication, we define mitocans (many of which have been known for a long time) and classify them into several classes based on their molecular mode of action. We chose the targets that are of major importance from the point of view of their role in mitochondrial destabilisation by small compounds, some of which are now trialled as anti-cancer agents. The classification starts with targets at the surface of mitochondria and ending up with those in the mitochondrial matrix. The purpose of this review is to present in a concise manner the classification of compounds that hold a considerable promise as potential anti-cancer drugs.