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Cancers
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The Multidimensional Landscape of Pancreatic Cancer Research
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The Multidimensional Landscape of Pancreatic Cancer Research

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 5102

Special Issue Editors

Prof. Dr. Claude Chelala

E-Mail Website
Guest Editor
Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
Interests: cancer bioinformatics; precision medicine; biobanking; health informatics; pancreatic cancer
Prof. Dr. Hemant M. Kocher

E-Mail Website
Co-Guest Editor
1. Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
2. Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London E1 1BB, UK
3. Barts Pancreas Tissue Bank, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
Interests: pancreatic cancer stroma and tumour-stroma cross-talk

Special Issue Information

Dear Colleagues,

Pancreatic cancer is a death sentence for most of its patients, and it is projected to be one of the leading causes of cancer-related death. Advances in therapeutic interventions have done little to improve the survival statistics at this time. The factors responsible for the dismal prognoses for patients remain poorly understood.

Genomic analyses reveal a complex mutational landscape, but the biological basis for the aggressive nature of this malignancy remains largely unresolved. This lack of progress being made is frustrating to patients and their families, as well as to clinicians and researchers. New strategies are needed to provide insights into the mechanisms of progression and inform clinical disease management.

There are currently neither reliable screening tests nor effective therapeutic options for pancreatic cancer. Surgery remains the only curative treatment, but, with up to 85% of patients presenting with vascular dissemination and distant metastases, only a small subset of patients is eligible for this surgical procedure. Long-term survival is uncommon even among patients with the best prognoses.  

Scant practical progress has been made in using molecular biomarkers to improve clinical patient management. There is therefore a demand for improved screening methods to identify localized tumors early, when clinical interventions would be more effective.

In this Special Issue, we invite papers focusing on improving our understanding of the clinical landscape of pancreatic cancer with a translational focus on early detection, progression, treatment, and prognosis. We encourage papers describing large multidimensional pancreatic cancer cohorts/biobanks to support researchers and provide them with tools to access and mine data. We also invite papers describing the use of machine learning and artificial intelligence on linked pancreatic cancer clinical, imaging, and molecular data.

This Special Issue addresses an area of urgent clinical need, will further boost our understanding of pancreatic carcinogenesis, and help unravel its dynamic clinical landscape to facilitate the promise of personalized medicine. We aim for it to be relevant to all patients, particularly the 85% of patients ineligible for surgery and whose current outcomes and treatment options are the poorest.

Prof. Dr. Claude Chelala
Prof. Dr. Hemant M. Kocher
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • early detection
  • prognosis
  • treatment
  • progression
  • biobanks
  • machine learning
  • artificial intelligence
  • electronic health records
  • health informatics
  • computational biology

Published Papers (4 papers)

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Research

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14 pages, 3573 KiB  
Article
Analyzing Flow Cytometry or Targeted Gene Expression Data Influences Clinical Discoveries—Profiling Blood Samples of Pancreatic Ductal Adenocarcinoma Patients
by Willem de Koning, Casper W. F. van Eijck, Fleur van der Sijde, Gaby J. Strijk, Astrid A. M. Oostvogels, Reno Debets, Casper H. J. van Eijck and Dana A. M. Mustafa
Cancers 2023, 15(17), 4349; https://doi.org/10.3390/cancers15174349 - 31 Aug 2023
Viewed by 1166
Abstract
Introduction: Monitoring the therapeutic response of pancreatic ductal adenocarcinoma (PDAC) patients is crucial to determine treatment strategies. Several studies have examined the effectiveness of FOLFIRINOX as a first-line treatment in patients with locally advanced pancreatic cancer, but little attention has been paid to [...] Read more.
Introduction: Monitoring the therapeutic response of pancreatic ductal adenocarcinoma (PDAC) patients is crucial to determine treatment strategies. Several studies have examined the effectiveness of FOLFIRINOX as a first-line treatment in patients with locally advanced pancreatic cancer, but little attention has been paid to the immunologic alterations in peripheral blood caused by this chemotherapy regimen. Furthermore, the influence of the measurement type (e.g., flow cytometry and targeted gene expression) on the clinical discoveries is unknown. Therefore, we aimed to scrutinize the influence of using flow cytometry or targeted immune gene expression to study the immunological changes in blood samples of PDAC patients who were treated with a single-cycle FOLFIRINOX combined with lipegfilgrastim (FFX-Lipeg). Material and Methods: Whole-blood samples from 44 PDAC patients were collected at two time points: before the first FOLFIRINOX cycle and 14 days after the first cycle. EDTA blood tubes were used for multiplex flow cytometry analyses to quantify 18 immune cell populations and for complete blood count tests as the standard clinical routine. The flow cytometry data were analyzed with FlowJo software. In addition, Tempus blood tubes were used to isolate RNA and measure 1230 immune-related genes using NanoString Technology®. Data quality control, normalization, and analysis were performed using nSolver™ software and the Advanced Analysis module. Results: FFX-Lipeg treatment increased the number of neutrophils and monocytes, as shown by flow cytometry and complete blood count in concordance with elevated gene expression measured via targeted gene expression profiling analysis. Interestingly, flow cytometry analysis showed an increase in the number of B and T cells after treatment, while targeted gene expression analysis showed a decrease in B and T cell-specific gene expression. Conclusions: Targeted gene expression complements flow cytometry analysis to provide a comprehensive understanding of the effects of FFX-Lipeg. Flow cytometry and targeted gene expression showed increases in neutrophils and monocytes after FFX-Lipeg. The number of lymphocytes is increased after treatment; nevertheless, their cell-specific gene expression levels are downregulated. This highlights that different techniques influence clinical discoveries. Therefore, it is important to carefully select the measurement technique used to study the effect of a treatment. Full article
(This article belongs to the Special Issue The Multidimensional Landscape of Pancreatic Cancer Research)
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11 pages, 552 KiB  
Article
15-Year Experience of Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) for Pancreatic Cancer—A Korean Nationwide Investigation
by So Jeong Yoon, Sang-Jae Park, Yoo-Seok Yoon, Tae-Ho Hong, Jin-Young Jang, Hee Joon Kim, Jin Seok Heo, Dae Wook Hwang and In Woong Han
Cancers 2023, 15(15), 3850; https://doi.org/10.3390/cancers15153850 - 28 Jul 2023
Cited by 1 | Viewed by 989
Abstract
Background: As systemic treatment for pancreatic cancer advances, distal pancreatectomy with celiac axis resection (DP-CAR) has been considered a curative-intent surgical option for advanced pancreatic cancer. This study aimed to review the surgical and oncologic outcomes of patients undergoing DP-CAR based on Korean [...] Read more.
Background: As systemic treatment for pancreatic cancer advances, distal pancreatectomy with celiac axis resection (DP-CAR) has been considered a curative-intent surgical option for advanced pancreatic cancer. This study aimed to review the surgical and oncologic outcomes of patients undergoing DP-CAR based on Korean nationwide data. Methods: We collected the data of patients who underwent DP-CAR for pancreatic cancer between 2007 and 2021 at seven major hospitals in Korea. The clinicopathological characteristics, postoperative complications, and data on the survival of the patients were retrospectively reviewed. Logistic regression analysis was performed to identify risk factors for postoperative complications and survival. Results: A total of 75 patients, consisting mainly of borderline resectable (n = 32) or locally advanced (n = 30) pancreatic cancer, were included in the analysis. Forty-two (56.0%) patients underwent neoadjuvant treatment (NAT). Twenty (26.7%) patients experienced Clavien–Dindo grade ≥ 3 complications, including four patients with ischemic gastropathy, two with hepatic ischemia, and two procedure-related mortalities. Neoadjuvant chemotherapy increased the risk of postoperative complications (p = 0.028). The median recurrence-free and overall survival were 7 and 19 months, with a 5-year survival rate of 13% and 24%, respectively. In the NAT group, a decrease in CA 19-9 and the post-NAT maximum standardized uptake value (SUVmax) in positron emission tomography were associated with survival after surgical resection. Conclusions: Despite the possibility of major complications, DP-CAR could be a feasible option for achieving curative resection with fair survival outcomes in patients with borderline resectable or locally advanced pancreatic cancer. Further studies investigating the safety of the procedure and identifying proper surgical candidates with potential survival gains are necessary. Full article
(This article belongs to the Special Issue The Multidimensional Landscape of Pancreatic Cancer Research)
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22 pages, 6696 KiB  
Article
CTHRC1 Induces Pancreatic Stellate Cells (PSCs) into Myofibroblast-like Cancer-Associated Fibroblasts (myCAFs)
by Min Kyung Kang, Fen Jiang, Ye Ji Kim, Kyoungjin Ryu, Atsushi Masamune, Shin Hamada, Yun-Yong Park and Sang Seok Koh
Cancers 2023, 15(13), 3370; https://doi.org/10.3390/cancers15133370 - 27 Jun 2023
Cited by 2 | Viewed by 1931
Abstract
[BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular [...] Read more.
[BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1–PSCs–cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation. Full article
(This article belongs to the Special Issue The Multidimensional Landscape of Pancreatic Cancer Research)
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Review

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16 pages, 596 KiB  
Review
Towards a Simplified and Cost-Effective Diagnostic Algorithm for the Surveillance of Intraductal Papillary Mucinous Neoplasms (IPMNs): Can We Save Contrast for Later?
by Nicolò Brandi and Matteo Renzulli
Cancers 2024, 16(5), 905; https://doi.org/10.3390/cancers16050905 - 23 Feb 2024
Cited by 1 | Viewed by 531
Abstract
The increased detection of pancreatic cysts in recent years has triggered extensive diagnostic investigations to clarify their potential risk of malignancy, resulting in a large number of patients undergoing numerous imaging follow-up studies for many years. Therefore, there is a growing need for [...] Read more.
The increased detection of pancreatic cysts in recent years has triggered extensive diagnostic investigations to clarify their potential risk of malignancy, resulting in a large number of patients undergoing numerous imaging follow-up studies for many years. Therefore, there is a growing need for optimization of the current surveillance protocol to reduce both healthcare costs and waiting lists, while still maintaining appropriate sensibility and specificity. Imaging is an essential tool for evaluating patients with intraductal papillary mucinous neoplasms (IPMNs) since it can assess several predictors for malignancy and thus guide further management recommendations. Although contrast-enhanced magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) has been widely recommended by most international guidelines, recent results support the use of unenhanced abbreviated-MRI (A-MRI) protocols as a surveillance tool in patients with IPMN. In fact, A-MRI has shown high diagnostic performance in malignant detection, with high sensitivity and specificity as well as excellent interobserver agreement. The aim of this paper is, therefore, to discuss the current available evidence on whether the implementation of an abbreviated-MRI (A-MRI) protocol for cystic pancreatic lesion surveillance could improve healthcare economics and reduce waiting lists in clinical practice without significantly reducing diagnostic accuracy. Full article
(This article belongs to the Special Issue The Multidimensional Landscape of Pancreatic Cancer Research)
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