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Genetic Markers in Pancreatic Cancer
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Genetic Markers in Pancreatic Cancer

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (15 November 2019) | Viewed by 15449

Special Issue Editors

Dr. George Zogopoulos

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Guest Editor
The McGill University Health Centre and the Goodman Cancer Research Centre of McGill University, Montreal, QC 3450, Canada
Dr. Yifan Wang

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Guest Editor
The McGill University Health Centre and the Goodman Cancer Research Centre of McGill University, Montreal, QC 22001, Canada

Special Issue Information

Dear Colleagues,

Advances in next-generation sequencing technologies have facilitated the testing of patients with pancreatic cancer for susceptibility genes. Recent investigations have estimated that 5–10% of patients with pancreatic cancer harbor a mutation in a susceptibility gene. These findings have cancer screening implications for relatives, and provide a framework for the development of gene-based pancreatic cancer surveillance programs for individuals at risk. Researchers are also beginning to sub-classify pancreatic cancer, which may facilitate the stratification of patients into therapeutic subtypes. Moreover, mutations in pancreatic cancer susceptibility genes are implicated in these subclassifications of pancreatic cancer.

In this Special Issue of Genes, we extend an invitation for reviews on the current state of the genetics and genomics of pancreatic cancer; as well as original research articles that focus on the discovery of genetic variations or mutations as well as genomic tumor profiles, which could be used to distinguish clinically-relevant disease or predict therapeutic efficacies and outcomes.

Dr. George Zogopoulos
Dr. Yifan Wang
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. Genes 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 cancer
  • genetic and genomic markers
  • molecular profiling
  • genetic abnormalities

Published Papers (4 papers)

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Research

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16 pages, 2958 KiB  
Article
Integration of Bioinformatics Resources Reveals the Therapeutic Benefits of Gemcitabine and Cell Cycle Intervention in SMAD4-Deleted Pancreatic Ductal Adenocarcinoma
by Yao-Yu Hsieh, Tsang-Pai Liu, Chia-Jung Chou, Hsin-Yi Chen, Kuen-Haur Lee and Pei-Ming Yang
Genes 2019, 10(10), 766; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100766 - 28 Sep 2019
Cited by 17 | Viewed by 3306
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer. The five-year survival rate of PDAC is very low (less than 8%), which is associated with the late diagnosis, high metastatic potential, and resistance to therapeutic agents. The identification [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer. The five-year survival rate of PDAC is very low (less than 8%), which is associated with the late diagnosis, high metastatic potential, and resistance to therapeutic agents. The identification of better prognostic or therapeutic biomarker may have clinical benefits for PDAC treatment. SMAD4, a central mediator of transforming growth factor beta (TGFβ) signaling pathway, is considered a tumor suppressor gene. SMAD4 inactivation is frequently found in PDAC. However, its role in prognosis and therapeutics of PDAC is still unclear. In this study, we applied bioinformatics approaches, and integrated publicly available resources, to investigate the role of SMAD4 gene deletion in PDAC. We found that SMAD4 deletion was associated with poorer disease-free, but not overall, survival in PDAC patients. Cancer hallmark enrichment and pathway analysis suggested that the upregulation of cell cycle-related genes in SMAD4-deleted PDAC. Chemotherapy response profiling of PDAC cell lines and patient-derived organoids revealed that SMAD4-deleted PDAC was sensitive to gemcitabine, the first-line treatment for PDAC, and specific cell cycle-targeting drugs. Taken together, our study provides an insight into the prognostic and therapeutic roles of SMAD4 gene deletion in PDAC, and SMAD4 gene copy numbers may be used as a therapeutic biomarker for PDAC treatment. Full article
(This article belongs to the Special Issue Genetic Markers in Pancreatic Cancer)
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Review

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18 pages, 512 KiB  
Review
Building towards Precision Oncology for Pancreatic Cancer: Real-World Challenges and Opportunities
by Yifan Wang, Anna Lakoma and George Zogopoulos
Genes 2020, 11(9), 1098; https://doi.org/10.3390/genes11091098 - 21 Sep 2020
Cited by 10 | Viewed by 3015
Abstract
The advent of next-generation sequencing (NGS) has provided unprecedented insight into the molecular complexity of pancreatic ductal adenocarcinoma (PDAC). This has led to the emergence of biomarker-driven treatment paradigms that challenge empiric treatment approaches. However, the growth of sequencing technologies is outpacing the [...] Read more.
The advent of next-generation sequencing (NGS) has provided unprecedented insight into the molecular complexity of pancreatic ductal adenocarcinoma (PDAC). This has led to the emergence of biomarker-driven treatment paradigms that challenge empiric treatment approaches. However, the growth of sequencing technologies is outpacing the development of the infrastructure required to implement precision oncology as routine clinical practice. Addressing these logistical barriers is imperative to maximize the clinical impact of molecular profiling initiatives. In this review, we examine the evolution of precision oncology in PDAC, spanning from germline testing for cancer susceptibility genes to multi-omic tumor profiling. Furthermore, we highlight real-world challenges to delivering precision oncology for PDAC, and propose strategies to improve the generation, interpretation, and clinical translation of molecular profiling data. Full article
(This article belongs to the Special Issue Genetic Markers in Pancreatic Cancer)
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11 pages, 479 KiB  
Review
ATM Serine/Threonine Kinase and its Role in Pancreatic Risk
by Neha Nanda and Nicholas J. Roberts
Genes 2020, 11(1), 108; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11010108 - 17 Jan 2020
Cited by 20 | Viewed by 4163
Abstract
Next-generation sequencing has led to the recent discovery of several novel pancreatic cancer susceptibility genes. These genes include ataxia telangiectasia mutated (ATM), a serine/threonine kinase that is an integral component of DNA repair. Pathogenic germline ATM variants are frequently identified in [...] Read more.
Next-generation sequencing has led to the recent discovery of several novel pancreatic cancer susceptibility genes. These genes include ataxia telangiectasia mutated (ATM), a serine/threonine kinase that is an integral component of DNA repair. Pathogenic germline ATM variants are frequently identified in patients with pancreatic ductal adenocarcinoma (PDAC) with and without a family history of the disease. Loss of ATM is also a frequent somatic event in the development of PDAC. These discoveries have advanced our understanding of the genetic basis of pancreatic cancer risk and will impact patient care through appropriate patient–risk stratification; personalized screening and early detection efforts; and, for some, targeted therapy. Full article
(This article belongs to the Special Issue Genetic Markers in Pancreatic Cancer)
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22 pages, 685 KiB  
Review
Metastasis in Pancreatic Ductal Adenocarcinoma: Current Standing and Methodologies
by Marina Ayres Pereira and Iok In Christine Chio
Genes 2020, 11(1), 6; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11010006 - 19 Dec 2019
Cited by 28 | Viewed by 4533
Abstract
Pancreatic ductal adenocarcinoma is an extremely aggressive disease with a high metastatic potential. Most patients are diagnosed with metastatic disease, at which the five-year survival rate is only 3%. A better understanding of the mechanisms that drive metastasis is imperative for the development [...] Read more.
Pancreatic ductal adenocarcinoma is an extremely aggressive disease with a high metastatic potential. Most patients are diagnosed with metastatic disease, at which the five-year survival rate is only 3%. A better understanding of the mechanisms that drive metastasis is imperative for the development of better therapeutic interventions. Here, we take the reader through our current knowledge of the parameters that support metastatic progression in pancreatic ductal adenocarcinoma, and the experimental models that are at our disposal to study this process. We also describe the advantages and limitations of these models to study the different aspects of metastatic dissemination. Full article
(This article belongs to the Special Issue Genetic Markers in Pancreatic Cancer)
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