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Biomedicines
Special Issues
Diagnostic and Therapeutic Approach to Pancreatic Cancer
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Diagnostic and Therapeutic Approach to Pancreatic Cancer

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 16590

Special Issue Editor

Dr. Sanchita Rauth

E-Mail Website
Guest Editor
University of Nebraska Medical Center, Omaha, NE, USA
Interests: post-translational modifications; transcription factors; cancer biology

Special Issue Information

Dear Colleagues,

Pancreatic cancer (PC) ranks as the third leading cause of cancer-related deaths in the United States, with a dismal five-year survival rate of 10%. Owing to the asymptomatic nature of PC, 80% of patients are diagnosed at an advanced stage, making it one of the most lethal cancers. Emerging techniques for early detection and treatment approaches with novel systemic therapies may help to improve the outcomes for PC patients. Recently, immunotherapies, such as checkpoint inhibitors (CTLA-4, PDL1) have been investigated (either alone or combined with chemotherapy) for the treatment of PC; however, most have proven to be less effective. Another emerging area for PC treatment includes the targeting of tumor microenvironment. Given that PC consists of dense stroma and the PC microenvironment is highly immunosuppressive, molecules or mechanisms that are involved with PC microenvironment are, thus, under active investigation. Beyond these, DNA damage repair proteins (PARP) inhibitors have also been examined for their potential to treat PC. Another obstacle in the field of PC is the lack of methods for early detection of pancreatic tumors. Recent studies have focused on identifying biomarkers; however, no biomarkers have yet entered clinical trials. The process of understanding the early detection and management of PC is dependent on knowledge of the basic tumor biology as well as determining the disease course (such as risk factors, treatment response, and disease progression) at a population level.

Dr. Sanchita Rauth
Guest Editor

Manuscript Submission Information

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Keywords

  • pancreatic cancer
  • systemic therapy
  • immunotherapy
  • tumor microenvironment
  • biomarkers

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Published Papers (7 papers)

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Research

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16 pages, 4131 KiB  
Article
Comprehensive Analysis Identifies PKP3 Overexpression in Pancreatic Cancer Related to Unfavorable Prognosis
by Yan Du, Shuang Hou, Zhou Chen, Wancheng Li, Xin Li and Wence Zhou
Biomedicines 2023, 11(9), 2472; https://doi.org/10.3390/biomedicines11092472 - 6 Sep 2023
Cited by 1 | Viewed by 1516
Abstract
Plakophilin 3 (PKP3) affects cell signal transduction and cell adhesion and performs a crucial function in tumorigenesis. The current investigation evaluated the predictive significance and underlying processes of PKP3 within pancreatic cancer (PC) tissues. The assessment of differences in PKP3 expression was conducted [...] Read more.
Plakophilin 3 (PKP3) affects cell signal transduction and cell adhesion and performs a crucial function in tumorigenesis. The current investigation evaluated the predictive significance and underlying processes of PKP3 within pancreatic cancer (PC) tissues. The assessment of differences in PKP3 expression was conducted through an analysis of RNA-seq data acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, clinical samples were collected to validate the findings. The predictive significance of PKP3 was investigated by analyzing survival data derived from TCGA and clinical specimens. PKP3′s biological function was assessed via phenotypic experiments after the suppression of PKP3 expression within PC cells. Functional enrichment analysis, encompassing KEGG, GO, and GSEA, was employed to assess the underlying mechanism of PKP3. Immune infiltration analysis was conducted in the present investigation to determine the association between PKP3 and tumor-infiltrating immune cells (TICs). In PC tissues, PKP3 expression was abnormally upregulated and correlated with a negative prognosis in individuals with PC. PKP3 can promote the progression, migration, and invasive capacity of PC cells and is relevant to the regulation of the PI3K–Akt and MAPK signaling pathways. Immune infiltration analysis demonstrated that PKP3 impeded CD8+ T-cell infiltration and immune cytokine expression within the tumor microenvironment. The PKP3 protein was identified as a prospective independent predictive indicator and represents a viable approach for immunotherapy in the context of PC. PKP3 may impact prognosis by broadly inhibiting immune cell infiltration and promoting the activation of tumor-associated signaling pathways. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Approach to Pancreatic Cancer)
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19 pages, 3424 KiB  
Article
Anti-microRNA-1976 as a Novel Approach to Enhance Chemosensitivity in XAF1+ Pancreatic and Liver Cancer
by Tsai-Yen Lee, Chien-Jen Tseng, Jin-Wun Wang, Ching-Po Wu, Chin-Yuan Chung, Ting-Ting Tseng and Shao-Chen Lee
Biomedicines 2023, 11(4), 1136; https://doi.org/10.3390/biomedicines11041136 - 10 Apr 2023
Cited by 6 | Viewed by 1801
Abstract
The current cancer treatments using chemoagents are not satisfactory in terms of outcomes and prognosis. Chemoagent treatments result in cell death or arrest, but the accompanying cellular responses are not well-studied. Exosomes, which are extracellular vesicles secreted by living cells, might mediate cellular [...] Read more.
The current cancer treatments using chemoagents are not satisfactory in terms of outcomes and prognosis. Chemoagent treatments result in cell death or arrest, but the accompanying cellular responses are not well-studied. Exosomes, which are extracellular vesicles secreted by living cells, might mediate cellular responses through microRNAs. We found that miR-1976 was highly enriched in exosomes secreted after chemoagent treatment. We developed a novel approach for in situ mRNA target screening and discovered several miR-1976-specific mRNA targets, including the proapoptotic gene XAF1, which was targeted by miR-1976 and which suppressed chemoagent-induced cell apoptosis. Increased RPS6KA1 gene transcription was associated with the increase in its intronic pre-miR-1976 expression. Blockade of miR-1976 could enhance chemosensitivities of hepatoma and pancreatic cancer cells in an XAF1-dependent manner, as evidenced by increased levels of cell apoptosis, reduced IC50 in cell toxicity assays, and suppressed tumor growth in animal xenograft experiments in vivo. We propose that intracellular levels of miR-1976 determine chemosensitivity, and its blockade could be a novel strategy and potential therapeutic application in cancer treatment. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Approach to Pancreatic Cancer)
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13 pages, 1133 KiB  
Article
The Relationship between the Expression of GATA4 and GATA6 with the Clinical Characteristics and Prognosis of Resectable Pancreatic Adenocarcinoma
by Victoria Heredia-Soto, Laura Gutiérrez-Sainz, Ismael Ghanem, Laura Guerra, Elena Palacios, Marta de Uribe, Lucía Trilla-Fuertes, María de Miguel, Paloma Cejas, Laura Medina, José Miguel Calderón, David Viñal, Marta Mendiola and Jaime Feliu
Biomedicines 2023, 11(2), 252; https://doi.org/10.3390/biomedicines11020252 - 18 Jan 2023
Cited by 3 | Viewed by 2105
Abstract
GATA4 and GATA6 are transcription factors involved in the differentiation and development of PDAC. GATA6 expression is related to the classic molecular subtype, while its absence is related to the basal-like molecular subtype. The aim was to determine the clinical utility of IHC [...] Read more.
GATA4 and GATA6 are transcription factors involved in the differentiation and development of PDAC. GATA6 expression is related to the classic molecular subtype, while its absence is related to the basal-like molecular subtype. The aim was to determine the clinical utility of IHC determination of GATA4 and GATA6 in a series of patients with resected PDAC. GATA4 and GATA6 expression was studied by IHC in TMA samples of normal tissue, PanIN, tumor tissue and lymph node metastases from a series of 89 patients with resected PDAC. Its relationship with clinicopathologic variables and the outcome was investigated. Seventy-two (81%) tumors were GATA6+ and 37 (42%) were GATA4+. While GATA4 expression was reduced during tumor progression, GATA6 expression remained highly conserved, except in lymph node metastases. All patients with early stages and well-differentiated tumors were GATA6+. The absence of GATA4 expression was related to smoking. Patients with GATA4+ or GATA6+ tumors had significantly lower Ca 19.9 levels. The expression of GATA4 and GATA6 was related to DFS, being more favorable in the GATA4+/GATA6+ group. The determination of the expression of GATA4 and GATA6 by IHC is feasible and provides complementary clinical and prognostic information that can help improve the stratification of patients with PDAC. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Approach to Pancreatic Cancer)
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Review

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14 pages, 705 KiB  
Review
Advances in the Early Diagnosis of Pancreatic Ductal Adenocarcinoma and Premalignant Pancreatic Lesions
by Reiko Yamada, Junya Tsuboi, Yumi Murashima, Takamitsu Tanaka, Kenji Nose and Hayato Nakagawa
Biomedicines 2023, 11(6), 1687; https://doi.org/10.3390/biomedicines11061687 - 11 Jun 2023
Cited by 4 | Viewed by 2488
Abstract
Pancreatic cancer is one of the most lethal human malignancies, in part because it is often diagnosed at late stages when surgery and systemic therapies are either unfeasible or ineffective. Therefore, diagnosing pancreatic cancer in earlier stages is important for effective treatment. However, [...] Read more.
Pancreatic cancer is one of the most lethal human malignancies, in part because it is often diagnosed at late stages when surgery and systemic therapies are either unfeasible or ineffective. Therefore, diagnosing pancreatic cancer in earlier stages is important for effective treatment. However, because the signs and symptoms may be nonspecific and not apparent until the disease is at a late stage, the timely diagnoses of pancreatic cancer can be difficult to achieve. Recent studies have shown that selective screening and increased usage of biomarkers could improve the early diagnosis of pancreatic cancer. In this review, we discuss recent advancements in the early detection of pancreatic ductal carcinoma and precancerous lesions. These include innovations in imaging modalities, the diagnostic utility of various biomarkers, biopsy techniques, and population-based surveillance approaches. Additionally, we discuss how machine learning methods are being applied to develop integrated methods of identifying individuals at high risk of developing pancreatic disease. In the future, the overall survival of pancreatic cancer patients could be improved by the development and adoption of these new methods and techniques. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Approach to Pancreatic Cancer)
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22 pages, 1320 KiB  
Review
Therapeutic Approaches in Pancreatic Cancer: Recent Updates
by Lokender Kumar, Sanjay Kumar, Kumar Sandeep and Sanjay Kumar Singh Patel
Biomedicines 2023, 11(6), 1611; https://doi.org/10.3390/biomedicines11061611 - 1 Jun 2023
Cited by 10 | Viewed by 3344
Abstract
Cancer is a significant challenge for effective treatment due to its complex mechanism, different progressing stages, and lack of adequate procedures for screening and identification. Pancreatic cancer is typically identified in its advanced progression phase with a low survival of ~5 years. Among [...] Read more.
Cancer is a significant challenge for effective treatment due to its complex mechanism, different progressing stages, and lack of adequate procedures for screening and identification. Pancreatic cancer is typically identified in its advanced progression phase with a low survival of ~5 years. Among cancers, pancreatic cancer is also considered a high mortality-causing casualty over other accidental or disease-based mortality, and it is ranked seventh among all mortality-associated cancers globally. Henceforth, developing diagnostic procedures for its early detection, understanding pancreatic cancer-linked mechanisms, and various therapeutic strategies are crucial. This review describes the recent development in pancreatic cancer progression, mechanisms, and therapeutic approaches, including molecular techniques and biomedicines for effectively treating cancer. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Approach to Pancreatic Cancer)
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21 pages, 392 KiB  
Review
A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty?
by Maria Cristina Conti Bellocchi, Stefano Francesco Crinò, Giulia De Marchi, Nicolò De Pretis, Andrew Ofosu, Federico Caldart, Rachele Ciccocioppo and Luca Frulloni
Biomedicines 2023, 11(5), 1393; https://doi.org/10.3390/biomedicines11051393 - 8 May 2023
Cited by 5 | Viewed by 2183
Abstract
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia [...] Read more.
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Approach to Pancreatic Cancer)
25 pages, 453 KiB  
Review
Circulating Cell-Free Nucleic Acids as Biomarkers for Diagnosis and Prognosis of Pancreatic Cancer
by Anelis Maria Marin, Heloisa Bruna Soligo Sanchuki, Guilherme Naccache Namur, Miyuki Uno, Dalila Luciola Zanette and Mateus Nóbrega Aoki
Biomedicines 2023, 11(4), 1069; https://doi.org/10.3390/biomedicines11041069 - 1 Apr 2023
Cited by 2 | Viewed by 2365
Abstract
A lack of reliable early diagnostic tools represents a major challenge in the management of pancreatic cancer (PCa), as the disease is often only identified after it reaches an advanced stage. This highlights the urgent need to identify biomarkers that can be used [...] Read more.
A lack of reliable early diagnostic tools represents a major challenge in the management of pancreatic cancer (PCa), as the disease is often only identified after it reaches an advanced stage. This highlights the urgent need to identify biomarkers that can be used for the early detection, staging, treatment monitoring, and prognosis of PCa. A novel approach called liquid biopsy has emerged in recent years, which is a less- or non-invasive procedure since it focuses on plasmatic biomarkers such as DNA and RNA. In the blood of patients with cancer, circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) have been identified such as DNA, mRNA, and non-coding RNA (miRNA and lncRNA). The presence of these molecules encouraged researchers to investigate their potential as biomarkers. In this article, we focused on circulating cfNAs as plasmatic biomarkers of PCa and analyzed their advantages compared to traditional biopsy methods. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Approach to Pancreatic Cancer)
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