Preclinical evaluation of an endoscopic electroporation system

Background and study aims: Targeted delivery of specific chemotherapeutic drugs into tumors can be achieved by delivering electrical pulses directly to the tumor tissue. This causes a transient formation of pores in the cell membrane that enables passive diffusion of normally impermeant drugs. A novel device has been developed to enable the endoscopic delivery of this tumor permeabilizing treatment. The aim of the preclinical studies described here was to investigate the efficacy and safety of this nonthermal ablation system in the treatment of gastrointestinal cancer models.

Methods: Murine, porcine, and canine gastrointestinal tumors and tissues were used to assess the efficacy and safety of electroporation delivered through the special device in combination with bleomycin. Tumor cell death, volume, and overall survival were recorded.

Results: Murine tumors treated with electrochemotherapy showed excellent responses, with cell death being induced rapidly, mainly via an apoptotic-type mechanism. Use of the system in canine gastrointestinal cancers demonstrated successful local endoluminal tumor resolution, with no safety or adverse effects noted.

Conclusions: Electroporation via the new device in combination with bleomycin offers a nonthermal tumor ablative approach, and presents clinicians with a new option for the management of gastrointestinal cancers.

Publikationsverlauf

Eingereicht: 24. Juli 2014

Angenommen: 01. Dezember 2015

Artikel online veröffentlicht:
04. April 2016

• References

• 1 Ariffin AB, Forde PF, Jahangeer S. et al. Releasing pressure in tumors: what do we know so far and where do we go from here? A review. Cancer Res 2014; 74: 2655-2662
• 2 Mir LM. Therapeutic perspectives of in vivo cell electropermeabilization. Bioelectrochemistry 2001; 53: 1-10
• 3 Sersa G, Stabuc B, Cemazar M. et al. Electrochemotherapy with cisplatin: potentiation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients. Eur J Cancer 1998; 34: 1213-1218
• 4 Caraco C, Mozzillo N, Marone U. et al. Long-lasting response to electrochemotherapy in melanoma patients with cutaneous metastasis. BMC Cancer 2013; 13: 564
• 5 Marty M, Sersa G, Garbay JR. et al. Electrochemotherapy – An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. Eur J Cancer Suppl 2006; 4: 3-13
• 6 Sersa G, Stabuc B, Cemazar M. et al. Electrochemotherapy with cisplatin: the systemic antitumour effectiveness of cisplatin can be potentiated locally by the application of electric pulses in the treatment of malignant melanoma skin metastases. Melanoma Res 2000; 10: 381-385
• 7 Whelan MC, Larkin JO, Collins CG. et al. Effective treatment of an extensive recurrent breast cancer which was refractory to multimodal therapy by multiple applications of electrochemotherapy. Eur J Cancer Suppl 2006; 4: 32-34
• 8 Miklavcic D, Sersa G, Brecelj E. et al. Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors. Med Biol Eng Comput 2012; 50: 1213-1225
• 9 Matthiessen LW, Johannesen HH, Hendel HW. et al. Electrochemotherapy for large cutaneous recurrence of breast cancer: a phase II clinical trial. Acta Oncol 2012; 51: 713-721
• 10 Larkin JO, Collins CG, Aarons S. et al. Electrochemotherapy: aspects of preclinical development and early clinical experience. Ann Surg 2007; 245: 469-479
• 11 Soden DM, Larkin JO, Collins CG. et al. Successful application of targeted electrochemotherapy using novel flexible electrodes and low dose bleomycin to solid tumours. Cancer letters 2006; 232: 300-310