Abstract
Simple SummaryThis review aims to highlight the potential of cold plasma, the fourth state of matter, as anti-cancer treatment for pancreatic cancer, and the importance of pancreatic stellate cells in the response to this treatment. Currently, a significant lack of basic research on cold plasma considering both pancreatic cancer and stellate cells exists. However, co-cultures of these populations can be advantageous, as they resemble the cell-to-cell interactions occurring in a tumor in response to therapy. Even more, these studies should be performed prior to clinical trials of cold plasma to avoid unforeseen responses to treatment. This review article provides a framework for future research of cold plasma therapies for pancreatic cancer, considering the critical role of pancreatic stellate cells in the disease and treatment outcome.Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with low five-year survival rates of 8% by conventional treatment methods, e.g., chemotherapy, radiotherapy, and surgery. PDAC shows high resistance towards chemo- and radiotherapy and only 15–20% of all patients can have surgery. This disease is predicted to become the third global leading cause of cancer death due to its significant rise in incidence. Therefore, the development of an alternative or combinational method is necessary to improve current approaches. Cold atmospheric plasma (CAP) treatments could offer multiple advantages to this emerging situation. The plasma-derived reactive species can induce oxidative damage and a cascade of intracellular signaling pathways, which could lead to cell death. Previous reports have shown that CAP treatment also influences cells in the tumor microenvironment, such as the pancreatic stellate cells (PSCs). These PSCs, when activated, play a crucial role in the propagation, growth and survival of PDAC tumors. However, the effect of CAP on PSCs is not yet fully understood. This review focuses on the application of CAP for PDAC treatment and the importance of PSCs in the response to treatment.
Highlights
To date, cancer remains as a highly complex group of diseases characterized by the disrupted metabolic activity, altered repair mechanisms, and redundant signaling pathways across various cell types [1]
As Cold atmospheric plasma (CAP) research progresses towards the development of future therapies, it is important to consider the role of other cell types in the tumor microenvironment (TME) of Pancreatic ductal adenocarcinoma (PDAC), such as the pancreatic stellate cells (PSCs), prior to considering clinical trials
Research in this field is still in an early stage, this review highlights the potential of CAP treatment for PDAC, as demonstrated in the state-of-the-art section, and shows that more research in this field is necessary
Summary
Cancer remains as a highly complex group of diseases characterized by the disrupted metabolic activity, altered repair mechanisms, and redundant signaling pathways across various cell types [1]. The interaction of cancer cells with other cells in the tumor microenvironment (TME) can determine the treatment outcome. Hard-to-kill cancers have highly developed properties that cause invasiveness, metastasis, and resistance towards therapy, among others One of these aggressive cancers is pancreatic cancer, which is predicted to become the third global leading cause of death by cancer in the near future [9]. As CAP research progresses towards the development of future therapies, it is important to consider the role of other cell types in the TME of PDAC, such as the PSCs, prior to considering clinical trials. Further studies of the complex interactions of cells in the TME of PDAC in vitro and in vivo will help to more accurately predict CAP treatment outcomes
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