Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors

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.

Electroporation: characteristics and therapeutic application of the method (a review)

“…Имеется положительный опыт применения различных технологий электропорации при почечно-клеточной кар-циноме [46], раке предстательной железы [47,48], мелано-ме кожи и ее метастазах [49,50], опухолях мозга [51,52].…”

“…Внутримышечная электропорация гена KGF со-провождалась стимуляцией пролиферации легочного эпи-телия и протекцией депрессии функции легких у мышей с моделированной эмфиземой [54]. Метод электропораци-онной терапии в экспериментальной и клинической меди-цине используется и по другим направлениям [51,[55][56][57][58].…”

Bipolar radiofrequency ablation with 2 × 2 electrodes as a building block for matrix radiofrequency ablation:Ex vivoliver experiments and finite element method modelling

“…Incomplete ablation not only leads to local recurrence but may render a tumour even more aggressive than before [46][47][48][49][50][51]. The limitations of RFA continue to stimulate the development of alternative ablation techniques such as cryoablation [52], laser-induced thermotherapy [53], microwave ablation [13,54], irreversible electroporation [55] and electrochemotherapy [56].…”

Modeling electroporation of the non-treated and vacuum impregnated heterogeneous tissue of spinach leaves

“…Depending on the amplitude and duration of the applied electric field, electroporation may occur in two forms: irreversible (Phillips, Maor, & Rubinsky, 2011;Rowan, MacGregor, Anderson, Fouracre, & Farish, 2000) or reversible (Glaser, Leikin, Chernomordik, Pastushenko, & Sokirko, 1988;Miklavčič, Serša, Brecelj, Gehl, Soden, Bianchi, et al, 2012). For either purpose, theoretical studies coupled with experimental investigation contribute to the understanding of events taking place in cells and tissues during electroporation.…”