Combination of cold plasma and pulsed electric fields – A rationale for cancer patients in palliative care

Cancer continues to be a significant threat to human health. Oncotherapy, therefore, relies on the combination of different approaches to increase a patient's chances. If therapeutic options are exhausted, effective palliation can at least still improve the quality of life. Over two decades ago, electrochemotherapy (ECT), which is based on pulsed electric field (PEF) exposures, was introduced in palliative care to alleviate the burden imposed by tumors, such as malignant melanoma and breast cancer. In this case, pulsed electric fields with a duration in the range of microseconds permeabilize cell membranes and permit reducing dosages of cytotoxic drugs and accordingly of associated systemic side effects. More recently, exposures to pulsed electric fields, shorter than the cellular plasma membrane charging time, have been found to affect subcellular structures and cell functions directly, i.e., without additional drugs. Instead of cytotoxic drugs, also the delivery of genes and calcium is currently investigated for alternative treatment options. Another way to induce tumor cell death is the introduction and/or generation of reactive species in the cellular environment by the application of cold physical plasma, resulting in the activation of redox signaling pathways. These latest developments encourage considering new treatment options. Of particular interest might be the possibility to promote the uptake of plasma-generated species by the combination with PEF-exposures. Hence, we review the latest developments in clinical and experimental ECT and PEF research in oncology and rationalize a combined treatment with plasmas for palliative therapy in patients.