Molecular effects of cyclosporine and oncogenesis:: a new model

Cyclosporine A is the most commonly used immunosuppressive agent during organ transplantation. One of the most feared adverse effects of cyctosporine A is the appearance of de novo cancers. The mechanisms that lead to the genesis of such cancers are thought to be only related to a side effect of cyclosporine A: a depressed immune system. Here, we review different molecular effects induced by cyclosporine A (inhibition of DNA repair, synthesis of TGF Beta, induction of apoptosis of activated T cells, inhibition of apoptosis through the inhibition of the opening of the mitochondrial Permeability Transition Pore) and propose that cyclosporine A can promote the genesis and the spread of cancer not only because of immunosuppression but also because of its ability to facilitate DNA mutations accumulation, to diminish the clearance of altered cells and to transform cancer cells into aggressive cancer cells. This new insights into the mechanisms of genesis of cyclosporine A-related cancers should be taken into account to develop preventive strategies or new immunosuppressive strategies. (C) 2004 Published by Elsevier Ltd.