The blood–brain barrier (BBB) plays an important protective role in the central nervous system and maintains its homeostasis. It regulates transport into brain tissue and protects neurons against the toxic effects of substances circulating in the blood. However, in the case of neurological diseases or primary brain tumors, i.e., gliomas, the higher permeability of the blood-derived substances in the brain tissue is necessary. Currently applied methods of treatment for the primary brain neoplasms include surgical removal of the tumor, radiation therapy, and chemotherapy. Despite the abovementioned treatment methods, the prognosis of primary brain tumors remains bad. Moreover, chemotherapy options seem to be limited due to low drug penetration into the cancerous tissue. Modulation of the blood–brain barrier permeability may contribute to an increase in the concentration of the drug in the CNS and thus increase the effectiveness of therapy. Interestingly, endothelial cells in cerebral vessels are characterized by the presence of adenosine 2A receptors (A2AR). It has been shown that substances affecting these receptors regulate the permeability of the BBB. The mechanism of increasing the BBB permeability by A2AR agonists is the actin-cytoskeletal reorganization and acting on the tight junctions. In this case, the A2AR seems to be a promising therapy target. This article aims to assess the possibility of increasing the BBB permeability through A2AR agonists to increase the effectiveness of chemotherapy and to improve the results of cancer therapy.

In this study, irreversible electroporation (IRE), electrochemotherapy (ECT), and calcium electroporation (CaEP) techniques were investigated as new strategies for human pancreatic cancer. Qualification of the patients, best "therapeutic moment" for each patient, safety, and complications after procedures were examined. In this pilot study were included 13 patients in this study, which were operated on in different pancreatic cancer stages. Patients underwent IRE or ECT with intravenous admission of cisplatin or electroporation with calcium intratumoral administration. The IRE procedure was safe for the patients. Medium overall survival for IRE, IRE + CTH, and IRE + CaCl₂ was respectively: 16, 29.5, and 19 months comparing to 10 months in control chemotherapy (CTH) group. Thus, IRE, ECT, and CaEP can be effective strategies for pancreatic cancer treatment.

(1) Background: In the last two decades, anticancer treatment has been extensively developed based on various physical methods, including electroporation (EP). On the basis of many in vitro and in vivo studies, electroporation and further electrochemotherapy (ECT) have been established as a treatment method for cutaneous and subcutaneous lesions. In this procedure, after placing electrodes in the tumor mass and the generation of electrical pulses, a reversible or irreversible rearrangement of the cell membrane occurs. Calcium electroporation has already been applied to treat skin tumors and subcutaneous tissue tumors. Here, we demonstrate the first application of irreversible electroporation (IRE) in combination with calcium ions and chemotherapy for patients with cancer. (2) Methods: This study aimed to present and compare the findings and outcomes of patients with locally advanced pancreatic adenocarcinoma who were qualified for the procedure. Two patients were treated with IRE with calcium ions after chemotherapy (paclitaxel + Gemcitabine (GCB) or FOLOX) or only FOLFOX (folinic acid calcium folinate, fluorouracil, and oxaliplatin). The clinicopathological data, overall survival, and the safety of the procedure were analyzed. (3) Results: Two patients were treated with calcium electroporation. One of the patients developed pancreatitis and the second developed pancreatic fistula, but both of them continued standard systemic treatment. Overall survival was 9 months in the first case and 21 months in the second case (and the patient is still alive). Calcium electroporation had a good impact on QOL (Quality of Life). (4) Conclusions: IRE accompanied chemotherapy, and intratumoral calcium ions administration might represent an additional therapy to surgery and chemotherapy in patients with locally advanced pancreatic cancer (LAPC), particularly in unresectable cases. However, further studies of randomized trials should be undertaken to elucidate the role of chemotherapy in IRE protocols.

According to the National Cancer Registry, 3486 people (1744 men and 1742 women) were diagnosed with pancreatic adenocarcinoma in Poland in 2018, resulting in 4908 deaths (2396 men and 2512 women). The only chance of successful treatment is through surgical resection, which is possible in only 20-30% of patients (stage I, II and some stage III cases).The remaining 70-80% of patients are those with stage III and IV disease, for whom resection is not possible. Mean survival in these patients is approx. 10.4 months (stage III). In the recent decade, an innovative method called electroporation, which involves destabilization of the cell membrane, has been established. This process can be reversible (RE) or irreversible (IRE), and leads to cell death. The ability to change membrane permeability has led to the development of novel methods involving electrochemotherapy (ECT) and calcium electroporation (CaEP) to treat solid tumors. In this study, both ECT and CaEP will be used to treat pancreatic cancer patients with poor prognosis. For each patient, the best "therapeutic moment" for the procedure will be selected based on the therapeutic protocol. Patients will receive reversible and irreversible electroporation (control arm-group A), CaEP (active arm-group B), or ECT with intravenous and intratumoral administration of bleomycin (active arm-group C) randomized 1:1:1. The primary endpoints will be progression-free survival (PFS) and patients' quality of life (QOL) assessed using the EORTC-PAN 26 scale. Secondary endpoints will be patient overall survival (OS), body weight, pain level, and levels of biomarkers such as Ca 19-9. The Irreversible Electroporation, ELectrochemotherapy and Calcium electroporation (IREC) study is necessary to examine the safety and efficiency of irreversible electroporation, electrochemotherapy and calcium electroporation in pancreatic cancer treatment.