Abstract
Electrochemotherapy, a combination of high voltage electric pulses and of an anticancer drug, has been demonstrated to be highly effective in treatment of cutaneous and subcutaneous tumors. Unique properties of electrochemotherapy (e.g., high specificity for targeting cancer cells, high degree of localization of treatment effect, capacity for preserving the innate immune response and the structure of the extracellular matrix) are facilitating its wide spread in the clinics. Due to high effectiveness of electrochemotherapy in treatment of cutaneous and subcutaneous tumors regardless of histological origin, there are now attempts to extend its use to treatment of internal tumors. To advance the applicability of electrochemotherapy to treatment of internal solid tumors, new technological developments are needed that will enable treatment of these tumors in daily clinical practice. New electrodes through which electric pulses are delivered to target tissue need to be designed with the aim to access target tissue anywhere in the body. To increase the probability of complete tumor eradication, the electrodes have to be accurately positioned, first to provide an adequate extent of electroporation of all tumor cells and second not to damage critical healthy tissue or organs in its vicinity. This can be achieved by image guided insertion of electrodes that will enable accurate positioning of the electrodes in combination with patient-specific numerical treatment planning or using a predefined geometry of electrodes. In order to be able to use electrochemotherapy safely for treatment of internal tumors located in relative proximity of the heart (e.g., in case of liver metastases), the treatment must be performed without interfering with the heart’s electrical activity. We describe recent technological advances, which allow treatment of liver and bone metastases, soft tissue sarcomas, brain tumors, and colorectal and esophageal tumors. The first clinical experiences in these novel application areas of electrochemotherapy are also described.
Highlights
ElectroporationWhen a cell is exposed to an external electric field, a transmembrane voltage is induced on the cell membrane
F Tribute: We would like to dedicate this paper and acknowledge the outstanding contribution by Professor Gerald O’Sullivan to the field of cancer research and the clinical application of electroporation
We describe recent technological advances, which allow treatment of liver and bone metastases, soft tissue sarcomas, brain tumors, and colorectal and esophageal tumors
Summary
When a cell is exposed to an external electric field, a transmembrane voltage is induced on the cell membrane. The threshold for electroporation depends on numerous physical (e.g., cell size and shape), biological (e.g., cytoskeleton structure and membrane composition) and electrical parameters (e.g., amplitude, duration and number of pulses, pulse repetition frequency), it is possible to achieve electroporation in vitro and in vivo regardless of the cell or tissue type [69]. This universal effectiveness of electroporation has made it a popular technique for loading cells with substances that are otherwise not possible or difficult to transfer into the cells. Applications such as gene transfection for gene therapy [16] and DNA vaccination [61], and electrochemotherapy for treatment of skin melanoma metastasis, skin recurrences of breast cancer, head and neck tumors and other histological types have been reported [27, 41, 42, 50, 64]
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