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Overcoming the Barriers: Cellular and Molecular Pathology of Pancreatic Cancer

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

Deadline for manuscript submissions: 31 December 2026 | Viewed by 1722

Special Issue Editor


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Guest Editor
Experimental Oncology Department, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
Interests: metastasis; tumor microenvironment; drug repurposing

Special Issue Information

Dear Colleagues,

Pancreatic cancer remains one of the most aggressive and treatment-resistant malignancies. Its dense and immunosuppressive tumor microenvironment (TME), metabolic adaptations, and early metastatic spread contribute to limited therapeutic success. This Special Issue aims to highlight basic, translational, and clinical research that advances our understanding of pancreatic tumor biology and paves the way for more effective interventions.

We are pleased to invite studies dissecting cellular and molecular mechanisms that shape immune exclusion, immune exhaustion, stromal barriers, cytokine networks, and tumor-derived suppressive signals in pancreatic cancer. We also seek studies that explore metabolic vulnerabilities such as ferroptosis, autophagy, redox homeostasis, nutrient scavenging pathways, and stromal–tumor metabolic crosstalk. Work identifying metabolic targets that sensitize tumors to immunotherapy, chemotherapy, or targeted agents is of particular interest. We also invite contributions focused on the molecular drivers of dissemination, dormancy, and colonization, as well as therapeutic strategies designed to eliminate or reprogram metastatic progenitors. We also encourage submissions reporting novel models for studying pancreatic cancer, including advanced organoid systems, co-culture platforms, engineered stromal models, and patient-derived xenografts.

This Special Issue aims to assemble a comprehensive and forward-looking collection of studies that deepen mechanistic insight and drive translational advances.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) immune cell dysfunction; stromal barriers; cytokine-signaling or chemokine pathways; cellular and molecular interactions within the TME; stromal remodeling; extracellular matrix biology and tumor–stromal communication; metabolic vulnerabilities and pathway targeting; mechanisms driving dissemination, dormancy, and colonization; organoids; co-culture systems; and microenvironment-mimicking platforms.

I look forward to receiving your contributions.

Dr. Jelena Grahovac
Guest Editor

Manuscript Submission Information

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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

  • pancreatic cancer
  • metastasis
  • tumor microenvironment
  • tumor metabolism
  • tumor immunity

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Published Papers (1 paper)

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Research

20 pages, 2721 KB  
Article
A Novel Mouse Model to Identify Antigen-Specific Immune Responses in Pancreatic Cancer Cachexia
by Ayushi Das, Debasmita Mukherjee, Liliana D’Alesio, Jessica Wedig, Hannah Lathrop, Maria Schmidt, Abigail Guenther, Morgan Kaiser, Jeon Varghese, Bryan Remaily, Samuel K. Kulp, Jeovanna Lowe, Jill A. Rafael-Fortney, Justin Thomas, Kyeongmin Kim, Adeoluwa Adeluola, Stacey Culp, Andrew Gunderson, Mitch A. Phelps, Christopher C. Coss and Thomas A. Maceadd Show full author list remove Hide full author list
Cancers 2026, 18(4), 587; https://doi.org/10.3390/cancers18040587 - 11 Feb 2026
Viewed by 1420
Abstract
Background: Pancreatic Ductal Adenocarcinoma (PDAC) has a dismal five-year survival rate of 13% and is closely associated with cachexia. Cancer cachexia is a multifactorial syndrome characterized by irreversible wasting of skeletal muscles, fat loss and systemic inflammation. While cachexia is known to confer [...] Read more.
Background: Pancreatic Ductal Adenocarcinoma (PDAC) has a dismal five-year survival rate of 13% and is closely associated with cachexia. Cancer cachexia is a multifactorial syndrome characterized by irreversible wasting of skeletal muscles, fat loss and systemic inflammation. While cachexia is known to confer resistance to immune checkpoint inhibition in several cancers, the bidirectional relationship between cachexia and the immune system in PDAC remains unclear, necessitating the development of novel preclinical models. Our laboratory has characterized a novel pancreatic cancer cachexia model in C57BL/6J mice by utilizing the pancreatic cancer cell line called KPCL-4 derived from KPC-LSIY mice (KrasLSL-G12D/+Tp53LSL-R172H/+Pdx1-Cre/R26LSL-LSIY). Methods: KPCL-4 cells were orthotopically injected into the pancreas of male and female C57BL/6J mice and hallmarks of cachexia were assessed at endpoint by measurement of tumor weight, terminal tumor-adjusted body weight, skeletal muscle, adipose tissue, liver and spleen masses, proteolytic markers and grip strength. Plasma cytokine and chemokine concentrations were quantified by Luminex assay and high-dimensional flow cytometry was used to investigate changes in tumor-infiltrating immune populations. Results: We observed a sex bias in cachexia presentation despite similar tumor weights in male and female mice, whereby males exhibited a >5% decrease in terminal tumor-adjusted body weight (p < 0.001), >50% fat loss (p < 0.001), upregulation of proteolytic markers in skeletal muscles (p < 0.01) and reduction in skeletal muscle mass (p < 0.05), function (p < 0.01) and cross-sectional area (p < 0.0001) whereas females demonstrated conserved skeletal muscle mass with 33% fat loss (p < 0.05), reduction in muscle cross-sectional area (p < 0.0001) and splenomegaly (p < 0.01). While intra-tumoral immune populations did not exhibit sex-specific differences, plasma cytokine concentrations were differentially upregulated in males and females, suggesting functional differences in immune cells as potent drivers of sex bias in KPCL-4-driven cachexia. Conclusions: The KPCL-4 orthotopic PDAC model exhibits prominent hallmarks of cachexia and serves as a novel platform for investigating the complex interplay between cancer cachexia and immunomodulation. Full article
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