Abstract
Pancreatic cancer represents a major challenge in oncology. Poor permeability of the pancreas and resistance to currently available therapies are impediments to improved patient survival. By transiently increasing cell membrane porosity and increasing drug uptake, Electrochemotherapy (ECT) has the potential to overcome these issues. In this study, we have evaluated the response of human and murine pancreatic cancer cells, in vitro, to electroporation in combination with Bleomycin, Cisplatin, or Oxaliplatin (ECT). The cytotoxic actions of all three drugs are potentiated when combined with electroporation in these cells. The biochemical and morphological changes post ECT are associated with immunogenic cell death that occurs with necroptosis rather than apoptosis. Moreover, ECT-induced cell death is rescued by Nec-1 suggesting that necroptosis may play a role in cell death mediated by cancer therapies.
Highlights
Pancreatic cancer (PC) is the fourth leading cause of cancer-related death with only a 6% survival at five years
We initially examined the ability of human (PANC-1) and murine (Pan02) pancreatic cancer cell lines to recover and form colonies following reversible electroporation
Bleomycin was one of the very first clinically approved drugs to be delivered with electroporation, with intracellular concentrations increasing by as much as 1000-fold in electrochemotherapy treated cells [15]
Summary
Pancreatic cancer (PC) is the fourth leading cause of cancer-related death with only a 6% survival at five years. There are few effective therapeutic options available to improve patient survival [1,2]. Surgery still remains the only treatment modality with the potential for cure but due to the generally late diagnoses, more than 80% of these cancers are inoperable [3]. For patients with these tumours, palliative chemotherapy regimens are offered. Chemotherapy offers marginal survival benefits due to the high chemoresistance of pancreatic cancer [4]. Few therapies have shown efficacy in the past and even standard of care therapies, like Gemcitabine (GEM) yield only modest improvements in the mortality of patients with advanced or metastatic disease
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