Declan M Soden PhD, Cork Cancer Research Centre

Local tumour control is a critically important part in the treatment of malignant solid tumours as it relieves symptoms, prevents complications, facilitates responsiveness to other systemic therapies and can often be curative. The EndoVe device has been developed at the Cork Cancer Research Centre and allows for an endoscopic cancer ablation treatment, which can target colorectal, gastric and oesophageal cancers by applying a brief electric pulse to the tumour. This greatly enhances tissue permeability maximizing the local/tumor absorption of chemotherapy drugs. As delivery is targeted, there is a reduction of over 90% of the chemotherapy drug (bleomycin) required resulting in significant benefits for patients including ease of treatment and minimal side effects.

Absorption occurs only in the area that has been treated with the electrical field and therefore is targeted to the tumour, leaving surrounding healthy tissues unaffected. One of the significant advantages of the system is that healthy cells and tissues surrounding the tumour are selectively less sensitive than the cancer cells to the treatment. A small percentage of healthy cells may undergo programmed cell death / apoptosis but a significant inflammatory reaction is not induced.
This approach to cancer treatment has become established in the treatment of skin cancers and is referred to as electrochemotherapy. The application of short, intense square wave pulses of direct current to skin tumors has been demonstrated to result in up to a 10 fold log increase in the intracellular concentration of bleomycin. Systemic toxicity and collateral injury is minimal as cytotoxicity is restricted to the tissues covered by the applied electrical field. Because the resulting cell death is by apoptosis there is minimal inflammatory reaction or systemic illness during involution of the tumor.
The first use of electrochemotherapy in humans was conducted on head and neck tumor nodules (Mir et al. Cancer; 1993). Over the last decade, studies using these systems have established ECT to be safe and effective in treating all cutaneous and subcutaneous lesions (Marty et al., European Journal of Cancer Supplements, 4: 3-13, 2006). The system has proven effective in cases where cancers were either unsuitable or unresponsive to surgery, chemotherapy or radiotherapy.

Experience to date has however been confined to cutaneous malignancies, often recurrent and metastatic after multimodal therapies. The treatment is minimally disturbing for patients, is easy to perform in an outpatient setting and is inexpensive. The real potential for this treatment however may exist through facilitating a minimally invasive approach to cancer ablation and this has consequently led to the development of the EndoVe device. The endoscopic attachment was designed to facilitate the treatment of internal cancers and a significant amount of preclinical large animal data has been prepared which demonstrates a significant opportunity for patient care

The treatment of spontaneous canine colorectal cancers has demonstrated the EndoVe device to be effective and safe with complete tumor ablation noted in the two inoperable cases treated to date. All procedures were conducted as a simple colonoscopy type procedure with no adverse side effects recorded. A Phase I clinical trial has been approved by the Irish Medicines Board and the study is due to commence in early 2010.