Selective targeting of mitochondria for the treatment of cancer.
Extract: Mitochondria fuel cellular activities via the production of ATP. They help control calcium levels within the cell and produce reactive oxygen species that function in cell signaling. The increased permeability of the mitochondrial membranes, known as permeabilization, is one stage, a point of no return, in the death of a cell. The mitochondrion is an attractive drug target because agents that seek and destroy mitochondria should be less prone to the perils of drug resistance. The trick is being able to selectively target mitochondria in one cell type and not another. This is now proving to be possible. When cells wake up from a period of inactivity with a burst of reproductive zeal, their mitochondrial function changes. This allows scientists to selectively target the mitochondria in certain cellular settings. Small positively-charged molecules accumulate at higher concentrations in the mitochondria of carcinomas, the most common type of solid tumor, due to bioenergetic differences between normal and cancerous cells. Most cancer treatments employ agents to interfere with cell division. Recently, growth signals that drive the proliferation and survival of tumor cells and tumor blood vessels have been successfully targeted. Mitochondria are the focal point for a variety of pro- and anti-apoptotic stimuli. The means by which tumor cells acquire resistance to apoptosis (cell suicide or programmed cell death) suggests that targeting of mitochondria or mitochondrial proteins may afford an effective means to circumvent the resistance of most tumor cells to apoptosis. Scientists are looking to exploit the pro-apoptotic function of mitochondria to trigger the death of cancer cells.
Dilda
Pierre J
PJ
Centre for Vascular Research, University of New South Wales and Department of Haematology, Prince of Wales Hospital, Sydney, NSW 2052, Australia.
Hogg
Philip J
PJ