scholarly journals Purinergic Signaling in Pancreas—From Physiology to Therapeutic Strategies in Pancreatic Cancer

2020 ◽  
Vol 21 (22) ◽  
pp. 8781
Author(s):  
Ivana Novak ◽  
Haoran Yu ◽  
Lara Magni ◽  
Ganga Deshar
Keyword(s):  
Pancreatic Cancer ◽  
Purinergic Signaling ◽  
Exocrine Secretion ◽  
Ductal Adenocarcinoma ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Pancreatic Cells ◽  
Pancreatic Exocrine ◽  
A Site ◽  
A2 Receptors

The purinergic signaling has an important role in regulating pancreatic exocrine secretion. The exocrine pancreas is also a site of one of the most serious cancer forms, the pancreatic ductal adenocarcinoma (PDAC). Here, we explore how the network of purinergic and adenosine receptors, as well as ecto-nucleotidases regulate normal pancreatic cells and various cells within the pancreatic tumor microenvironment. In particular, we focus on the P2X7 receptor, P2Y2 and P2Y12 receptors, as well as A2 receptors and ecto-nucleotidases CD39 and CD73. Recent studies indicate that targeting one or more of these candidates could present new therapeutic approaches to treat pancreatic cancer. In pancreatic cancer, as much as possible of normal pancreatic function should be preserved, and therefore physiology of purinergic signaling in pancreas needs to be considered.

scholarly journals New Aspects of the Epigenetics of Pancreatic Carcinogenesis

Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 18
Author(s):  
Murat Toruner ◽  
Martin E. Fernandez-Zapico ◽  
Christopher L. Pin
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Survival Rate ◽  
Epigenetic Mechanisms ◽  
Therapeutic Approaches ◽  
Cancer Epigenetics ◽  
Pancreatic Carcinogenesis ◽  
New Therapeutic Approaches ◽  
Environmental Events ◽  
Underlying Pathogenesis

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.

scholarly journals The Immune Microenvironment in Pancreatic Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7307 ◽  
Author(s):  
Magdalena Huber ◽  
Corinna U. Brehm ◽  
Thomas M. Gress ◽  
Malte Buchholz ◽  
Bilal Alashkar Alhamwe ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Stroma ◽  
Ductal Adenocarcinoma ◽  
Cancer Type ◽  
Cellular Interactions ◽  
Therapeutic Approaches ◽  
Immune Microenvironment ◽  
Cellular Immune

The biology of solid tumors is strongly determined by the interactions of cancer cells with their surrounding microenvironment. In this regard, pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) represents a paradigmatic example for the multitude of possible tumor–stroma interactions. PDAC has proven particularly refractory to novel immunotherapies, which is a fact that is mediated by a unique assemblage of various immune cells creating a strongly immunosuppressive environment in which this cancer type thrives. In this review, we outline currently available knowledge on the cross-talk between tumor cells and the cellular immune microenvironment, highlighting the physiological and pathological cellular interactions, as well as the resulting therapeutic approaches derived thereof. Hopefully a better understanding of the complex tumor–stroma interactions will one day lead to a significant advancement in patient care.

scholarly journals What Is Recent in Pancreatic Cancer Immunotherapy?

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Elena Niccolai ◽  
Domenico Prisco ◽  
Mario Milco D'Elios ◽  
Amedeo Amedei
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Advanced Disease ◽  
Active Immunotherapy ◽  
Therapeutic Approaches ◽  
Standard Chemotherapy ◽  
New Therapeutic Approaches ◽  
The Poor ◽  
Digestive Cancers

Pancreatic cancer (PC) represents an unresolved therapeutic challenge, due to the poor prognosis and the reduced response to currently available treatments. Pancreatic cancer is the most lethal type of digestive cancers, with a median survival of 4–6 months. Only a small proportion of PC patients is curative by surgical resection, whilst standard chemotherapy for patients in advanced disease generates only modest effects with considerable toxic damages. Thus, new therapeutic approaches, specially specific treatments such as immunotherapy, are needed. In this paper we analyze recent preclinical and clinical efforts towards immunotherapy of pancreatic cancer, including passive and active immunotherapy approaches, designed to target pancreatic-cancer-associated antigens and to elicit an antitumor responsein vivo.

scholarly journals Pancreatic Cancer Signaling Pathways, Genetic Alterations, and Tumor Microenvironment: The Barriers Affecting the Method of Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 373
Author(s):  
Darya Javadrashid ◽  
Amir Baghbanzadeh ◽  
Afshin Derakhshani ◽  
Patrizia Leone ◽  
Nicola Silvestris ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Immune Checkpoint ◽  
Therapeutic Strategy ◽  
Genetic Alterations ◽  
Ductal Adenocarcinoma ◽  
Therapeutic Approaches ◽  
Ras Mutation ◽  
Direct Targeting

Genetic alterations, especially the K-Ras mutation, carry the heaviest burden in the progression of pancreatic precursor lesions into pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment is one of the challenges that hinder the therapeutic approaches from functioning sufficiently and leads to the immune evasion of pancreatic malignant cells. Mastering the mechanisms of these two hallmarks of PDAC can help us in dealing with the obstacles in the way of treatment. In this review, we have analyzed the signaling pathways involved in PDAC development and the immune system’s role in pancreatic cancer and immune checkpoint inhibition as next-generation therapeutic strategy. The direct targeting of the involved signaling molecules and the immune checkpoint molecules, along with a combination with conventional therapies, have reached the most promising results in pancreatic cancer treatment.

scholarly journals Kallikrein-Related Peptidase 6 Is Associated with the Tumour Microenvironment of Pancreatic Ductal Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3969
Author(s):  
Juliana B. Candido ◽  
Oscar Maiques ◽  
Melanie Boxberg ◽  
Verena Kast ◽  
Eleonora Peerani ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Standard Of Care ◽  
Tumour Microenvironment ◽  
Ductal Adenocarcinoma ◽  
Therapeutic Approaches ◽  
Novel Treatments ◽  
Pancreatic Cancer Cells ◽  
Invasive Tumour ◽  
Mrna And Protein Expression

As cancer-associated factors, kallikrein-related peptidases (KLKs) are components of the tumour microenvironment, which represents a rich substrate repertoire, and considered attractive targets for the development of novel treatments. Standard-of-care therapy of pancreatic cancer shows unsatisfactory results, indicating the need for alternative therapeutic approaches. We aimed to investigate the expression of KLKs in pancreatic cancer and to inhibit the function of KLK6 in pancreatic cancer cells. KLK6, KLK7, KLK8, KLK10 and KLK11 were coexpressed and upregulated in tissues from pancreatic cancer patients compared to normal pancreas. Their high expression levels correlated with each other and were linked to shorter survival compared to low KLK levels. We then validated KLK6 mRNA and protein expression in patient-derived tissues and pancreatic cancer cells. Coexpression of KLK6 with KRT19, αSMA or CD68 was independent of tumour stage, while KLK6 was coexpressed with KRT19 and CD68 in the invasive tumour area. High KLK6 levels in tumour and CD68+ cells were linked to shorter survival. KLK6 inhibition reduced KLK6 mRNA expression, cell metabolic activity and KLK6 secretion and increased the secretion of other serine and aspartic lysosomal proteases. The association of high KLK levels and poor prognosis suggests that inhibiting KLKs may be a therapeutic strategy for precision medicine.

scholarly journals Current Immunotherapeutic Approaches in Pancreatic Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Shigeo Koido ◽  
Sadamu Homma ◽  
Akitaka Takahara ◽  
Yoshihisa Namiki ◽  
Shintaro Tsukinaga ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Approach ◽  
Standard Of Care ◽  
Small Population ◽  
Advanced Stage ◽  
Therapeutic Approaches ◽  
Gemcitabine Resistance ◽  
New Therapeutic Approaches ◽  
Pancreatic Cancer Cells ◽  
Promising Treatment

Pancreatic cancer is a highly aggressive and notoriously difficult to treat. As the vast majority of patients are diagnosed at advanced stage of the disease, only a small population is curative by surgical resection. Although gemcitabine-based chemotherapy is typically offered as standard of care, most patients do not survive longer than 6 months. Thus, new therapeutic approaches are needed. Pancreatic cancer cells that develop gemcitabine resistance would still be suitable targets for immunotherapy. Therefore, one promising treatment approach may be immunotherapy that is designed to target pancreatic-cancer-associated antigens. In this paper, we detail recent work in immunotherapy and the advances in concept of combination therapy of immunotherapy and chemotherapy. We offer our perspective on how to increase the clinical efficacy of immunotherapies for pancreatic cancer.

Apoptosis induced by microwave radiation in pancreatic cancer JF305 cells

2014 ◽  
Vol 92 (4) ◽  
pp. 324-329 ◽  
Author(s):  
Wenhe Zhu ◽  
Wei Zhang ◽  
Huiyan Wang ◽  
Junjie Xu ◽  
Yan Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Morphological Changes ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Dependent Manner ◽  
Therapeutic Approaches ◽  
Caspase 9 ◽  
New Therapeutic Approaches ◽  
Related Proteins ◽  
Dose Dependent

New therapeutic approaches are needed to improve the survival rate from pancreatic cancer, one of the most lethal human malignancies. In this study, JF305 cells were treated with microwaves at doses of 2.5, 5.0, 10.0, 15.0, and 20.0 mW/cm2 for 20 min. The inhibition of JF305 cell proliferation was tested using the MTT assay. Apoptotic cells were detected with Hoechst 33258 staining and a Nucleo-Counter NC-3000. The expression of apoptosis-related proteins was examined with Western blot. The results showed that microwaves inhibited the growth of JF305 cells in a dose–dependent manner, and caused morphological changes in apoptotic body formation. The percentages of apoptosis detected using annexin V–fluorescein isothiocyanate (FITC) were 4.0%, 10.0%, 12.0%, and 30.0% with the dosage of microwave (0, 5.0, 10.0, and 20.0 mW/cm2), respectively. Treatment with microwaves increased the activity of caspase-9 and caspase-3, down-regulated the expression of Bcl-2, and up-regulated the expression of Bax and CytoC. In addition, the expression level of p65 was increased whereas the level of IκBα down-regulated. Those results suggest that microwaves inhibit cell growth and induce apoptosis in JF305 cells through an NF-κB-regulated mitochondria-mediated pathway.

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