The Changing Landscape in Pancreatic Ductal Adenocarcinoma Management: From Tumor Biology to Clinical Practice

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 10290

Special Issue Editors


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Guest Editor
Department of Pharmacology, University of Thessaly, Biopolis, 41500 Larissa, Greece
Interests: cancer research; anticancer drug development; mouse models of cancer; xenografts; cell culture; natural products; small molecules
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Guest Editor
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
Interests: gastrointestinal malignancies; tumour microenvironment; prognostic biomarkers; chemotherapy toxicity; patient derived xenografts

Special Issue Information

Dear Colleagues, 

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer with little improvement in the survival rates over the past few decades. It is the fourth leading cause of cancer-related mortality in the USA and in Europe. The prognosis of patients with this disease remains unfavorable for all stages of disease, with the 5-year overall survival rate being <5%. Surgical resection, followed by adjuvant therapy, is the only radical therapeutic option; however, <15% of patients present with operable disease. Patients with advanced disease at presentation or recurrence may receive palliative chemotherapy, although the rates of response and survival benefit are modest. Aggressive tumor biology as well as primary or secondary drug resistance contribute significantly toward this dismal prognosis.

In this context, the aim of the current Special Issue is to bring to the scientific community’s attention new research and findings in the field of pancreatic cancer biology and therapeutic advances. It is the hope of the guest editors that this collection will result in new insights into this deleterious type of cancer and provide new information regarding the so many still unmet needs in the field.

The guest editors welcome all kinds of papers that could help the scientific community to advance in the field: original articles, reviews, case reports, and short reports of important findings are welcome.

We cordially invite researchers working in the field to contribute original research articles as well as critical review articles, case reports, and short reports of important findings that can shed more light in the fight against pancreatic cancer.

Dr. Konstantinos Dimas
Dr. Konstantinos Kamposioras
Guest Editors

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Keywords

  • pancreatic cancer
  • pancreatic cancer biology
  • new drugs
  • mechanism of action
  • pharmacodynamics
  • pharmacokinetics
  • biomarkers
  • tumor microenvironment
  • targeted therapies
  • immunotherapy
  • resistance

Published Papers (3 papers)

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Research

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10 pages, 2414 KiB  
Article
Bioinformatic Analysis of the BCL-xL/BCL2L1 Interactome in Patients with Pancreatic Cancer
by Dimitrios E. Magouliotis, Anna P. Karamolegkou, Prokopis-Andreas Zotos, Evangelos Tatsios, Athina A. Samara, Dimitra Alexopoulou, Fani Koutsougianni, Nikos Sakellaridis, Dimitris Zacharoulis and Konstantinos Dimas
Medicina 2022, 58(11), 1663; https://doi.org/10.3390/medicina58111663 - 17 Nov 2022
Cited by 1 | Viewed by 1581
Abstract
Objectives: The aim of the present study was to analyze the differential gene expression of BCL-xL/BCL2L and the associated genetic, molecular, and biologic functions in pancreatic ductal adenocarcinoma (PDAC) by employing advanced bioinformatics to investigate potential candidate genes implicated in the pathogenesis [...] Read more.
Objectives: The aim of the present study was to analyze the differential gene expression of BCL-xL/BCL2L and the associated genetic, molecular, and biologic functions in pancreatic ductal adenocarcinoma (PDAC) by employing advanced bioinformatics to investigate potential candidate genes implicated in the pathogenesis of PDAC. Materials and Methods: Bioinformatic techniques were employed to build the gene network of BCL-xL, to assess the translational profile of BCL-xL in PDAC, assess its role in predicting PDAC, and investigate the associated biologic functions and the regulating miRNA families. Results: Microarray data extracted from one dataset was incorporated, including 130 samples (PDAC: 69; Control: 61). In addition, the expression level of BCL-xL was higher in PDAC compared to control samples (p < 0.001). Furthermore, BCL-xL demonstrated excellent discrimination (AUC: 0.83 [95% Confidence Intervals: 0.76, 0.90]; p < 0.001) and calibration (R squared: 0.31) traits for PDAC. A gene set enrichment analysis (GSEA) demonstrated the molecular functions and miRNA families (hsa-miR-4804-5p, hsa-miR-4776-5p, hsa-miR-6770-3p, hsa-miR-3619-3p, and hsa-miR-7152-3p) related to BCL-xL. Conclusions: The current findings unveil the biological implications of BCL-xL in PDAC and the related molecular functions and miRNA families. Full article
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Review

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19 pages, 742 KiB  
Review
Management of Advanced Pancreatic Cancer through Stromal Depletion and Immune Modulation
by Tiantong Liu, Sihang Cheng, Qiang Xu and Zhiwei Wang
Medicina 2022, 58(9), 1298; https://doi.org/10.3390/medicina58091298 - 17 Sep 2022
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Abstract
Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Unfortunately, therapeutic gains in the treatment of other cancers have not successfully translated to pancreatic cancer treatments. Management of pancreatic cancer is difficult due to the lack of effective therapies and [...] Read more.
Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Unfortunately, therapeutic gains in the treatment of other cancers have not successfully translated to pancreatic cancer treatments. Management of pancreatic cancer is difficult due to the lack of effective therapies and the rapid development of drug resistance. The cytotoxic agent gemcitabine has historically been the first-line treatment, but combinations of other immunomodulating and stroma-depleting drugs are currently undergoing clinical testing. Moreover, the treatment of pancreatic cancer is complicated by its heterogeneity: analysis of genomic alterations and expression patterns has led to the definition of multiple subtypes, but their usefulness in the clinical setting is limited by inter-tumoral and inter-personal variability. In addition, various cell types in the tumor microenvironment exert immunosuppressive effects that worsen prognosis. In this review, we discuss current perceptions of molecular features and the tumor microenvironment in pancreatic cancer, and we summarize emerging drug options that can complement traditional chemotherapies. Full article
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20 pages, 420 KiB  
Review
Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy
by Laurentia Gales, Leyla Forsea, Diana Mitrea, Irina Stefanica, Irina Stanculescu, Radu Mitrica, Mihai Georgescu, Oana Trifanescu, Rodica Anghel and Luiza Serbanescu
Medicina 2022, 58(9), 1239; https://doi.org/10.3390/medicina58091239 - 07 Sep 2022
Cited by 10 | Viewed by 5776
Abstract
Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients’ daily treatment for [...] Read more.
Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients’ daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patient’s daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes; mebendazole, as an anthelmintic; atorvastatin, as a cholesterol-lowering drug; propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimental/lack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma. Full article
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