Electrochemotherapy - Electroporation Based Medical Treatment
University of Ljubljana, Slovenia
Faculty of Electrical Engineering
Department of Biomedical Engineering
Vendredi 23 novembre 2011
Amphi 3 - Faculté de Médecine, 22 av. Camille Desmoulins - Brest
When a cell is exposed to an external electric field, a transmembrane voltage is induced on the cell membrane and if sufficiently high, permeabilization (termed also electroporation) of the cell membrane occurs, i.e. hydrophilic pores form in the membrane and flow of molecules in and out of the cell increases substantially. Electroporation can be irreversible leading to cell death or reversible when membrane reseals and cells survive. Electroporation is used in clinical applications, such as nonthermal irreversible electroporation for tissue ablation, gene transfection for gene therapy and DNA vaccination and electrochemotherapy for treatment of skin melanoma metastases, skin recurrences of breast cancer, and other skin cancers.
Electrochemotherapy is a local cancer treatment, where short and intense electric pulses are delivered to tumour nodules in vivo using appropriate electrodes in order to transiently electroporate membranes of cancer cells and thus enable direct access to the cytosol. Hence anticancer drug, such as bleomycin, which is hydrophilic and lacks efficient uptake mechanisms, can readily enter the cell. Once inside, bleomycin acts as an enzyme, creating several single and double strand DNA breaks. Another cytotoxic drug successfully used in electrochemotherapy is cisplatin, which is a low permeant drug causing cell apoptosis. These cytotoxic drugs affect only rapidly dividing cancer cells and not normal cells in the surrounding tissue. The unique properties of electrochemotherapy (i.e. high specificity for targeting cancer cells, capacity for preserving the innate immune response and the structure of the extracellular matrix) assure high therapeutic index thus facilitating wide spread of electrochemotherapy in clinics. Electrochemotherapy proved efficient in treatment of cutaneous and subcutaneous tumours regardless of their histological origin. Because of its demonstrated efficacy, electrochemotherapy is being developed for treatment of internal solid tumours. For this purpose, new technological developments are needed that will enable safe and efficient treatment of internal tumours. In general, success of treatment depends on the volume where electroporation occurs, which can be determined by distribution of sufficiently high electric field strength and controlled by appropriate positioning of electrodes and applied amplitude of electric pulses. To increase the probability of complete tumour eradication, the electrodes have to be accurately positioned, first, to provide electroporation of all tumour cells, and second, not to damage critical healthy tissue or organs in vicinity. This can be achieved by patient-specific numerical treatment planning and image guided insertion of electrodes that enables their adequate positioning.