A Powerhouse approach to Cancer treatment: Targeting Mitochondria

Drug targeting is defined as the ability of a drug molecule to accumulate in the target organ or tissue selectively such that the concentration of the drug at the disease site is high, while its concentration in nontarget organs and tissues is low, preferably, below certain minimal level to prevent any toxic effect.

Role of the Mitochondria that plays in human health and disease has rendered many contributions to the field of "Mitochondrial Medicine". Their main function is to supply the adenosine triphosphate (ATP). Their main job is to oxidizing glucose to provide energy for the cell. The process makes ATP and is called cellular respiration. Therefore, mitochondria are known as "the powerhouse of the cell.

Molecules located on or inside mitochondria are considered prime pharmacological targets and a wide range of efforts are underway to exploit these targets to develop targeted therapies for various diseases including cancer. Mitochondria are known to play a key role in the complex apoptotic mechanism and trigger cell death via several mechanisms that include disrupting electron transport and energy metabolism, releasing or activating proteins that mediate apoptosis and altering cellular redox potential.

The selective accumulation approach to targeting mitochondria of cancer cells

This approach requires two levels of specific accumulation; drug accumulation in the tumor and then drug accumulation in the mitochondria of cancer cells.

·         Molecular modification approaches for selective accumulation in mitochondria

·         Nanocarrier based approaches for selective accumulation in mitochondria

There are numerous molecules currently in use or being tested in clinical trials that act on mitochondria. Several clinically approved anticancer drugs such as paclitaxel, VP-16 and vinorelbine as well as an increasing number of experimental anticancer drugs such as, ceramide, MKT077 and CD437 acid have been found to act directly on mitochondria to trigger apoptosis.

As discussed so far, targeting mitochondrial molecules in the development of cancer therapy relies on the two basic interpretations of targeting via selective action on the target and selective accumulation at the target site where the term target must represent a molecule and not a tissue or cell location.