Ru Chen, Xinhua Chen and Stephen J Beebe
Surgery as resection or transplantation remains a fundamental means for cancer treatment and often offers an opportunity for a cure. However, surgery is not always possible because of tumor proximity to blood vessels or ducts or when a patient is not healthy enough to undergo surgery. Application of nanosecond pulsed electric fields (nsPEFs) is a new approach to treat cancer using pulse power technology that was originally designed for military purposes. This novel approach deposits extremely short pulses of high power, low energy electric fields into malignant tissues using electrodes to encompass tumors. Pre-clinical studies show that treatments are effective and without local or systemic side effects, including absences of scarring. Pre-clinical trials for basal cell carcinoma are completed, but results have not been published. For treating internal tumors, electric fields can be delivered by catheter electrodes and laparoscopy procedures. Here we present a review of the literature using nsPEFs for cancer ablation and present some recent work from the author’s laboratory. We demonstrate efficacy for treatment of an ectopic mouse (Hepa-1- 6) and an orthotopic rat (N1-S1) Hepatocellular Carcinoma (HCC). NsPEFs eliminate tumors by mechanisms in the presence of active caspases (apoptosis) as well as in absences of active caspases (necrosis/necroptosis). Treatment also breaches small vessels, but spares larger vessels and ducts. NsPEF treatments also reduce angiogenesis as determined by decreases in Vascular Endothelia Growth Factor (VEGF). Microvascular density markers (CD-31, CD-34 and CD-105) are significantly decreased after treatment, limiting new blood vessel formation and reinforcing tumor cell demise. Furthermore, initial challenge studies show that mice are resistant to re-introduction of the same tumor cells after treatment, suggesting that nsPEFs induces immunogenic cell death and possible host cell immune responses after treatment. NsPEF ablation of cancer targets at least three hallmarks of cancer (evasion of apoptosis, angiogenesis maintenance and immune surveillance) and provides an effective alternative or adjunct therapy for cancers in skin and internal organs.