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Biomedicines
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Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches 2.0
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Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 10339

Special Issue Editors

Prof. Dr. Rossano Lattanzio

E-Mail Website
Guest Editor
Department of Innovative Technologies in Medicine and Dentistry, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
Interests: pathology; oncology; molecular biomarkers; tumor molecular profiling; immunohistochemistry; prognosis; survival; metastatic relapse; targeted therapy; pancreatic adenocarcinoma; breast cancer; bladder cancer; colorectal cancer; lung cancer; prostate cancer; GBM; paraganglioma; thymic epithelial tumors; melanoma; pulmonary carcinoid; signal transduction; epigenetics; angiogenesis; extracellular matrix; epidermal growth factor receptors; antibody drug conjugate (ADC)
Prof. Dr. Konstantinos Dimas

E-Mail Website
Guest Editor
Department of Pharmacology, School of Medicine, School of Health Sciences, University of Thessaly, Larisa, Greece
Interests: cancer; natural products; small molecules; drug discovery and development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide, beause of the propensity of the tumors to disseminate at an early stage, sustained by their complex microenvironment. At the time of diagnosis, only 20% of PC patients are eligible for surgical resection. Resistance to chemotherapy represents the most important clinical challenge in PC, impacting patients' long-term outcomes strongly. Hence, there is an urgent need to find new therapeutic strategies that can be more specific and effective for treating PC patients. This Special Issue will provide insights regarding PC cells' molecular drivers, highlighting the impact of the tumor microenvironment on PC cells, and will discuss the implications for developing specific PC therapies. Authors are invited to submit their original research, communications, and review articles to this Special Issue of Biomedicines. Potential topics include, but are not limited to, the following:

-The role of cancer stem cells or tumor-initiating cells in the genesis and progression of PC

-The impact of the epigenetic changes in PC disease

-Pancreatic tumor microenvironment

-Role of the exosomes in PC

-Prognostic and predictive biomarkers in PC

-Novel targeted therapies in PC.

Prof. Dr. Rossano Lattanzio
Prof. Dr. Konstantinos Dimas
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pancreatic ductal adenocarcinoma
  • survival
  • targeted therapy
  • drug resistance
  • biomarkers
  • tumor microenvironment

Related Special Issues

Published Papers (4 papers)

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Research

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18 pages, 3713 KiB  
Article
Targeting Periostin Expression Makes Pancreatic Cancer Spheroids More Vulnerable to Natural Killer Cells
by Didem Karakas, Merve Erkisa, Remzi Okan Akar, Gizem Akman, Ezgi Yudum Senol and Engin Ulukaya
Biomedicines 2023, 11(2), 270; https://doi.org/10.3390/biomedicines11020270 - 19 Jan 2023
Cited by 3 | Viewed by 2237
Abstract
Pancreatic cancer (PaCa) characteristically has a dense tumor microenvironment, which results in poor patient prognosis. Pancreatic stellate cells (PSCs) are the most abundant cells in the PaCa microenvironment and the principal source of collagen. Periostin, a matricellular protein, is produced specifically by PSCs [...] Read more.
Pancreatic cancer (PaCa) characteristically has a dense tumor microenvironment, which results in poor patient prognosis. Pancreatic stellate cells (PSCs) are the most abundant cells in the PaCa microenvironment and the principal source of collagen. Periostin, a matricellular protein, is produced specifically by PSCs and promotes the aggressiveness of PaCa cells by facilitating extracellular collagen assembly. Here, we aimed to decrease extracellular collagen assembly by suppressing periostin, thereby increasing the cytotoxic activity of natural killer (NK) cells. Periostin expression was suppressed in PSCs (called PSC-P) using CRISPR-Cas9. PaCa cells (BxPC-3) were co-cultured with PSC and PSC-P cells in a 3D environment to form tumor spheroids mimicking the tumor microenvironment. The extracellular collagen production of spheroids was evaluated by Masson’s trichrome staining. The cytotoxic activity of NK-92 cells was analyzed by flow cytometry and confocal microscopy via CD107a staining. Cell death in BxPC-3 cells was evaluated by measuring Annexin-V and PI positivity using flow cytometry. As a result, periostin suppression decreased extracellular collagen and increased the infiltration of NK-92 cells into spheroids, and induced cell death in PaCa cells. In conclusion, we suggest that periostin might be a therapeutic target for PaCa and further analysis is warranted using in vivo models for proof-of-concept. Full article
(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches 2.0)
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14 pages, 2007 KiB  
Article
The FGFR2c/PKCε Axis Controls MCL-1-Mediated Invasion in Pancreatic Ductal Adenocarcinoma Cells: Perspectives for Innovative Target Therapies
by Danilo Ranieri, Deborah French, Flavia Persechino, Luisa Guttieri, Maria Rosaria Torrisi and Francesca Belleudi
Biomedicines 2022, 10(7), 1652; https://doi.org/10.3390/biomedicines10071652 - 09 Jul 2022
Cited by 1 | Viewed by 1378
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy whose main characterizations are Kirsten Rat Sarcoma-activating mutations (KRAS) and a highly aggressive phenotype. Based on our recent findings demonstrating that the highly aberrant expression of the mesenchymal isoform of Fibroblast Growth Factor Receptor 2 [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy whose main characterizations are Kirsten Rat Sarcoma-activating mutations (KRAS) and a highly aggressive phenotype. Based on our recent findings demonstrating that the highly aberrant expression of the mesenchymal isoform of Fibroblast Growth Factor Receptor 2 (FGFR2c) in PDAC cells activates Protein-Kinase C Epsilon (PKCε), which in turn controls receptor-mediated epithelial to mesenchymal transition (EMT), here we investigated the involvement of these signaling events in the establishment of additional tumorigenic features. Using PDAC cell lines expressing divergent levels of the FGFR2c and stable protein depletion approaches by short hairpin RNA (shRNA), we found that FGFR2c expression and its PKCε downstream signaling are responsible for the invasive response to Fibroblast Growth Factor 2 (FGF2) and for anchorage-independent growth. In addition, in vitro clonogenic assays, coupled with the check of the amount of cleaved Poly Adenosine Diphosphate-Ribose Polymerase 1 (PARP1) by Western blot, highlighted the involvement of both FGFR2c and PKCε in cell viability. Finally, monitoring of Myeloid Cell Leukemia 1 (MCL-1) expression and Sarcoma kinase family (SRC) phosphorylation suggested that the FGFR2c/PKCε axis could control cell migration/invasion possibly via MCL-1/SRC-mediated reorganization of the actin cytoskeleton. Being PKCs RAS-independent substrates, the identification of PKCε as a hub molecule downstream FGFR2c at the crossroad of signaling networks governing the main malignant tumor hallmarks could represent an important advance towards innovative target therapies overcoming RAS. Full article
(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches 2.0)
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10 pages, 2009 KiB  
Article
Multiplex Patient-Based Drug Response Assay in Pancreatic Ductal Adenocarcinoma
by Andrew Armstrong, Muhammad R. Haque, Sina Mirbagheri, Usman Barlass, Douglas Z. Gilbert, Jaimin Amin, Ajaypal Singh, Ankur Naqib and Faraz Bishehsari
Biomedicines 2021, 9(7), 705; https://doi.org/10.3390/biomedicines9070705 - 23 Jun 2021
Cited by 8 | Viewed by 3119
Abstract
Pancreatic ductal adenocarcinoma (PDA) is an extremely lethal malignancy arising from the pancreas. The treatment of PDA is complicated by ineffective treatments and a lack of biomarkers predictive of treatment success. We have designed a patient-derived organoid (PDO) based high-throughput drug screening assay [...] Read more.
Pancreatic ductal adenocarcinoma (PDA) is an extremely lethal malignancy arising from the pancreas. The treatment of PDA is complicated by ineffective treatments and a lack of biomarkers predictive of treatment success. We have designed a patient-derived organoid (PDO) based high-throughput drug screening assay to model treatment response to a variety of conventional and investigational treatments for PDA. Consecutive patients undergoing endoscopic ultrasound-guided fine-needle biopsy for tissue diagnosis of PDA at Rush University Medical Center were offered to participate in the study. Biopsies were immediately processed to develop organoids. Fifteen PDOs were screened for sensitivity to 18 compounds, including conventional PDA chemotherapies and FDA-approved investigational targeted therapies in cancer using Cell-titer GLO 3D (Promega) cell viability assay. The area under the curve (AUC) was calculated and normalized to the maximum area under the curve to generate a normalized AUC between 0 and 1. Molecular profiling of PDOs was conducted using RNA-seq. Human PDA transcriptomic was extracted from The Cancer Genome Atlas (TCGA). The drug response curves were reproducible. We observed variation in response to conventional therapies overall as well as among individual patients. There were distinct transcriptome signatures associated with response to the conventional chemotherapeutics in PDA. The transcriptomic profile of overall resistance to conventional therapies in our study was associated with poor survival in PDA patients in TCGA. Our pathway analysis for targeted drugs revealed a number of predictors of response associated with the mechanism of action of the tested drug. The multiplex organoid-based drug assay could be used in preclinical to inform patient stratification and therapeutic selection in PDA. When combined with omics data, ex vivo response to treatment could help identify gene signatures associated with response to novel therapies. Full article
(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches 2.0)
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Review

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19 pages, 571 KiB  
Review
Pancreatic Cancer Organoids: An Emerging Platform for Precision Medicine?
by Evangelia Sereti, Irida Papapostolou and Konstantinos Dimas
Biomedicines 2023, 11(3), 890; https://doi.org/10.3390/biomedicines11030890 - 14 Mar 2023
Cited by 6 | Viewed by 2719
Abstract
Despite recent therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with remarkable resistance to treatment, poor prognosis, and poor clinical outcome. More efficient therapeutic approaches are urgently needed to improve patients’ survival. Recently, the development of organoid culture [...] Read more.
Despite recent therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with remarkable resistance to treatment, poor prognosis, and poor clinical outcome. More efficient therapeutic approaches are urgently needed to improve patients’ survival. Recently, the development of organoid culture systems has gained substantial attention as an emerging preclinical research model. PDAC organoids have been developed to study pancreatic cancer biology, progression, and treatment response, filling the translational gap between in vitro and in vivo models. Here, we review the rapidly evolving field of PDAC organoids and their potential as powerful preclinical tools that could pave the way towards precision medicine for pancreatic cancer. Full article
(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches 2.0)
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