The basis of electrochemotherapy.

Antitumor electrochemotherapy is a treatment of solid tumors which combines a cytotoxic nonpermeant drug, like bleomycin, with locally delivered permeabilizing electric pulses (1-3). More generally, a new form of vectorization is achieved by the combination of nonpermeant molecules with intracellular targets and of a physical perturbation that locally permeabilizes the cells. This vectorization does not require chemical, biochemical or biological modifications of the targeted compound, since the modification is performed on the target cells. A very convenient way to transiently permeabilize the cells is the use of appropriate electric pulses (short and intense squarewave electric pulses) that are not cytotoxic by themselves (1). These electric pulses reversibly permeabilize the electropulsed cells. Consequently, they allow increased drug delivery inside cells, particularly in the case of drugs for which the plasma membrane is a barrier that limits their access inside the cell [termed nonpermeant drugs] (4). As illustrated in the various protocols reported in this volume, electrochemotherapy using bleomycin is efficient to eradicate subcutaneously transplanted and spontaneous small tumors in mice and rats as well as experimental internal tumors transplanted in rat brain or in rabbit or rat liver. All the clinical trials (3,5-10) confirm the efficacy of this new therapeutical approach based on an original way to deliver nonpermeant cytotoxic drugs.