Mechanisms of electrochemotherapy.

Electrochemotherapy is a new therapeutic approach providing delivery into cell interiors of nonpermeant drugs with intracellular targets. It is based on the local application of short and intense electric pulses that transiently permeabilize cells in tissues. To date, its main application has been the treatment of tumor nodules when the electric pulses are associated with nonpermeant drugs having high intrinsic cytotoxicity. The most convenient drug is bleomycin, a currently used anticancer drug, but cytotoxicity of cisplatin is also increased in vivo by means of this original drug delivery approach. The efficacy of this new method is based on the following mechanisms: (i) electropermeabilization of cells in tissues; (ii) use of nonpermeant drugs having a high intrinsic cytotoxicity; (iii) existence of vascular effects due to the permeabilizing electric pulses; (iv) complementary role of the host's immune system. Preclinical trials have shown the efficacy of this new therapeutic modality in various tumor models. Clinical trials are in progress, demonstrating its feasibility in humans as well as the interest of the method.