Preclinical studies on electrochemotherapy

Abstract

Electrochemotherapy is the combination of chemotherapy and local application of electric pulses. Application of electric pulses, i.e., electroporation, is used as a means to increase drug delivery to cells. Electrochemotherapy has the potential to improve the efficacy of drugs that have impeded transport through the plasma membrane. While enhancement has been demonstrated for some chemotherapeutic drugs that were tested, only cisplatin and bleomycin have been evaluated clinically. Recently, calcium electroporation has also entered clinical testing. The increased cytotoxicity of bleomycin and cisplatin was demonstrated by exposure of cells to electric pulses in vitro, and potentiation of their antitumor effectiveness in vivo was also demonstrated. Preclinical studies have explored several different parameters that could affect effectiveness of electrochemotherapy, such as the dose and route of drug administration, timing of application of electric pulse, and coverage of the tumor with electric field. These aspects were all evaluated on different primary or transplanted tumors models in mice, rats, and hamsters. Most importantly, the underlying mechanisms of electrochemotherapy were explored, from increased drug uptake to vascular effects and involvement of immune system. These findings enabled swift translation of electrochemotherapy into human and veterinary oncology