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Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors
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Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors

A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (30 June 2026) | Viewed by 13781

Editor

Dr. Makoto Abue

E-Mail Website
Guest Editor
Departments of Gastroenterology, Miyagi Cancer Center, Nodayama 47-1, Medeshima-Shiote, Natori, Miyagi, Japan
Interests: pancreatic cancer; biomarkers; diagnosis; prognosis; liquid biopsy; proteomics; metabolomics

Special Issue Information

Dear Colleagues,

With our Special Issue, titled "Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors", we hope to shape the future of pancreatic cancer care and strive towards improved patient outcomes. For this Special Issue, we invite submissions on cutting-edge research in the field of pancreatic cancer diagnosis and prognosis, thereby contributing to advancements that will ultimately enhance patient prognosis. Topics of interest include the following: novel biomarkers (liquid biopsy, proteomics, metabolomics, etc.); established and emerging prognostic factors (tumor microenvironment, genetic alterations, and inflammatory markers); and their clinical implications for early detection, risk stratification, and personalized management. Submissions in forms of original research articles, reviews, and perspectives are welcome. Please submit your manuscripts by June 2026, so we collectively work toward a brighter future for pancreatic cancer patients.

We look forward to your submissions.

Dr. Makoto Abue
Guest Editor

Manuscript Submission Information

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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
  • biomarkers
  • diagnosis
  • prognosis
  • liquid biopsy
  • proteomics
  • metabolomics
  • tumor microenvironment
  • genetic aberrations/mutations
  • inflammatory markers

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Published Papers (7 papers)

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Research

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17 pages, 7121 KB  
Article
Multicenter Validation of Foundation Model Adaptation for Automated Pancreatic Tumor Delineation on CT Scans
by Halil Ertugrul Aktas, Eminenur Sen Tasci, Linkai Peng, Muhammed Enes Tasci, Yavuz B. Taktak, Sitki Safa Taflan, Baver Tutun, Fergan Bol, Murat Iren, Mucahit Ekici, Andrea Mia Bejar, Elif Keles, Hongyi Pan, Wanying Dou, Burak Gultekin, Alper Akin, Oyku Ikizgul, Okan Cetin, Emre Uysal, Maide Mureva, Mustafa Orhan Nalbant, Nurullah Kaya, Alpay Medetalibeyoglu, Kadir Atakir, Berna Akkus Yildirim, Gulbiz Dagoglu Kartal, Zongwei Zhou, Sukru Mehmet Erturk, Frank H. Miller, Gorkem Durak and Ulas Bagciadd Show full author list remove Hide full author list
Cancers 2026, 18(17), 2836; https://doi.org/10.3390/cancers18172836 - 1 Sep 2026
Viewed by 363
Abstract
Background: Accurate pancreatic tumor segmentation on contrast-enhanced computed tomography (CECT) is important for staging, treatment planning, and response assessment in pancreatic ductal adenocarcinoma (PDAC). Although foundation models have shown promise for medical image segmentation, their effectiveness for disease-specific tumor delineation remains uncertain. [...] Read more.
Background: Accurate pancreatic tumor segmentation on contrast-enhanced computed tomography (CECT) is important for staging, treatment planning, and response assessment in pancreatic ductal adenocarcinoma (PDAC). Although foundation models have shown promise for medical image segmentation, their effectiveness for disease-specific tumor delineation remains uncertain. This study evaluated whether fine-tuning a Segment Anything Model (SAM)-based framework on the target cohorts improves pancreatic tumor segmentation compared with directly applied foundation models. Methods: In this retrospective multicenter study, CECT examinations from patients with pathologically confirmed PDAC acquired between 2015 and 2025 were included. Two foundation model baselines, nnInteractive and MedSAM2, were compared with three TAGS-based configurations representing increasing levels of adaptation: TAGS (Zero-Shot), SAM-TAGS (fine-tuned from SAM weights), and MSD-TAGS (fine-tuned from a pancreas-specific checkpoint). Performance was assessed using patient-level five-fold cross-validation with the Dice Similarity Coefficient (DSC) and Normalized Surface Dice (NSD). A leave-one-center-out analysis was additionally performed to evaluate generalization to institutions absent from training. Results: A total of 500 patients with PDAC from four independent centers were included. MSD-TAGS achieved the highest overall segmentation performance, with a mean DSC of 0.703 and a mean NSD of 0.835. SAM-TAGS achieved a mean DSC of 0.691 and a mean NSD of 0.822. In comparison, nnInteractive achieved a mean DSC of 0.632 and a mean NSD of 0.782; MedSAM2, 0.585 and 0.792; and TAGS (Zero-Shot), 0.496 and 0.639, respectively. Compared with each competing method, MSD-TAGS achieved significantly higher DSC and NSD values (all Holm-adjusted p < 0.001). It also achieved the highest DSC across all four centers and the highest NSD in three of the four centers. Under leave-one-center-out evaluation, MSD-TAGS declined by 0.025 DSC and SAM-TAGS by 0.089. Conclusions: Task-specific adaptation improved pancreatic tumor segmentation with foundation models, and fine-tuned TAGS outperformed two publicly released promptable models applied without adaptation. Models initialized from a pancreas-specific checkpoint showed greater robustness under center-held-out evaluation. These findings support the importance of organ-specific initialization and target-cohort fine-tuning for disease-specific segmentation and warrant further validation before clinical translation. The multicenter pancreatic tumor CT segmentation dataset, including de-identified images and expert segmentation annotations, is publicly available to facilitate future research. Full article
(This article belongs to the Special Issue Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors)
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18 pages, 3028 KB  
Article
Hypercoagulability Predicts Survival and Reflects NET-Associated Thromboinflammation in Advanced Pancreatic Cancer
by Lingaku Lee, Masami Miki, Masayuki Hijioka, Terumasa Hisano, Rie Sugimoto and Masayuki Furukawa
Cancers 2026, 18(13), 2120; https://doi.org/10.3390/cancers18132120 - 30 Jun 2026
Viewed by 514
Abstract
Background: Cancer-associated thrombosis is a major complication in pancreatic cancer; however, its true burden and prognostic significance remain unclear, largely owing to under-detection of asymptomatic events. In addition, the clinical relevance of cancer-related hypercoagulability and neutrophil extracellular traps (NETs), which may link [...] Read more.
Background: Cancer-associated thrombosis is a major complication in pancreatic cancer; however, its true burden and prognostic significance remain unclear, largely owing to under-detection of asymptomatic events. In addition, the clinical relevance of cancer-related hypercoagulability and neutrophil extracellular traps (NETs), which may link thrombosis and tumor biology, has not been adequately evaluated in advanced pancreatic cancer. Methods: In this prospective study, newly diagnosed patients with unresectable pancreatic ductal adenocarcinoma underwent systematic screening for venous thromboembolism (VTE) at baseline, followed by longitudinal surveillance. Circulating coagulation markers and NET-related biomarkers were analyzed. Associations among VTE, hypercoagulability, NET-related biomarkers, and overall survival (OS) were evaluated. Results: Among 134 patients, VTE was detected at diagnosis in 28.4%, with the majority being asymptomatic. Hypercoagulability and NET-related biomarkers were significantly associated with VTE occurrence. Patients with baseline VTE (6.2 vs. 12.1 months, p = 0.002) and hypercoagulability (7.7 vs. 15.2 months, p = 0.002) demonstrated shorter OS. In multivariate analysis, hypercoagulability, but not baseline VTE, remained independently associated with inferior OS (hazard ratio 2.03, 95% confidence interval 1.27–3.27). Notably, the adverse prognostic impact of hypercoagulability was consistently observed across nearly all predefined clinical subgroups. Furthermore, a reduction in or normalization of D-dimer levels following anticoagulant therapy was associated with prolonged survival. Conclusions: Hypercoagulability, rather than overt thrombotic events, independently predicts survival outcomes in advanced pancreatic cancer. These findings support a biology-driven approach to thrombosis assessment and indicate that monitoring and therapeutic modulation of hypercoagulability may improve risk stratification and clinical management in this population. Full article
(This article belongs to the Special Issue Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors)
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12 pages, 1090 KB  
Article
Serum Levels of Soluble Forms of Fas and FasL in Patients with Pancreatic and Papilla of Vater Adenocarcinomas
by Stavros Anagnostoulis, Helen Bolanaki, Byron Asimakopoulos, Dimitrios Ouroumidis, Maria Koutini, Spyridon Patris, Ioannis Tzimagiorgis and Anastasios J. Karayiannakis
Cancers 2026, 18(1), 106; https://doi.org/10.3390/cancers18010106 - 29 Dec 2025
Viewed by 1080
Abstract
Objective: Impairment of the Fas/FasL apoptotic pathway is a mechanism contributing to the malignant transformation of multiple cell types. This study aimed to investigate the clinical and prognostic relevance of serum soluble Fas (sFas) and soluble Fas ligand (sFasL) levels in patients with [...] Read more.
Objective: Impairment of the Fas/FasL apoptotic pathway is a mechanism contributing to the malignant transformation of multiple cell types. This study aimed to investigate the clinical and prognostic relevance of serum soluble Fas (sFas) and soluble Fas ligand (sFasL) levels in patients with pancreatic and papilla of Vater adenocarcinomas. Methods: An ELISA was used to determine sFas and sFasL levels. Serum samples were obtained from 53 healthy controls, 82 pancreatic and 14 papilla of Vater carcinoma patients. Sera from carcinoma patients were obtained before surgery and 30 days after surgery. The relationships of preoperative levels with clinicopathological features and patient survival were evaluated. Changes in serum sFas and sFasL levels after surgery were also evaluated. Results: Higher sFas and lower sFasL levels were found in the serum of carcinoma patients in comparison to healthy controls. Serum sFas and sFasL levels correlated significantly with both lymph node and distant metastases and an advanced stage of disease. Elevated sFas and decreased sFasL levels correlated significantly with poor overall survival when the entire study population was considered with sFas being an independent prognostic factor. After patient stratification, their prognostic value was evident in pancreatic carcinoma patients only. Preoperative sFas levels decreased and sFasL levels increased after radical resection of the tumor but remained unchanged in cases of unresectable disease. Conclusions: These findings suggest that serum levels of sFas and sFasL could be useful tumor markers with prognostic value in pancreatic adenocarcinomas. Increased sFas secretion may reflect a mechanism for apoptotic escape of cancer cells. Full article
(This article belongs to the Special Issue Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors)
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Review

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15 pages, 3053 KB  
Review
Pancreatic Acinar Cell Carcinoma: A Rare Pancreatic Malignancy with Distinct Biology and Emerging Therapeutic Opportunities
by Noor Farhoud, Raed Moh’d Taiseer Al-Rajabi, Joaquina Celebre Baranda, Haoran Li, Wei Zhang, Ravi Kumar Paluri, Ashish Manne, Prasad Dandawate, Weijing Sun and Anup Kasi
Cancers 2026, 18(14), 2315; https://doi.org/10.3390/cancers18142315 - 17 Jul 2026
Viewed by 893
Abstract
Pancreatic acinar cell carcinoma (PACC) is a rare exocrine pancreatic malignancy accounting for approximately 1–2% of adult pancreatic neoplasms. Although historically grouped with pancreatic ductal adenocarcinoma (PDAC), accumulating evidence demonstrates that PACC represents a biologically distinct entity with unique clinical, pathologic, and molecular [...] Read more.
Pancreatic acinar cell carcinoma (PACC) is a rare exocrine pancreatic malignancy accounting for approximately 1–2% of adult pancreatic neoplasms. Although historically grouped with pancreatic ductal adenocarcinoma (PDAC), accumulating evidence demonstrates that PACC represents a biologically distinct entity with unique clinical, pathologic, and molecular characteristics. Compared with PDAC, PACC more commonly presents as a large pancreatic mass, is less frequently associated with obstructive jaundice, and exhibits lower rates of KRAS mutations. Recent genomic studies have identified recurrent alterations involving DNA damage repair pathways, WNT/β-catenin signaling, and actionable kinase fusions, including BRAF and RAF1 rearrangements. In advanced disease, fluoropyrimidine- and platinum-based regimens appear to demonstrate greater activity than traditional gemcitabine-based approaches, although prospective comparative data are lacking. This review summarizes the current understanding of the epidemiology, clinical presentation, pathology, molecular landscape, treatment approaches, and prognostic factors associated with PACC. We highlight emerging opportunities for precision oncology and discuss ongoing challenges in the management of this uncommon pancreatic malignancy. Full article
(This article belongs to the Special Issue Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors)
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25 pages, 852 KB  
Review
Genomic Biomarkers for First-Line Treatment Selection in Metastatic Pancreatic Ductal Adenocarcinoma: A Narrative Review
by Anushareddy Muddasani, Ahmed Abdelnoor and Ashish Manne
Cancers 2026, 18(10), 1664; https://doi.org/10.3390/cancers18101664 - 21 May 2026
Viewed by 1108
Abstract
Metastatic pancreatic ductal adenocarcinoma (PDAC) is typically treated with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel (GnP), but the choice between regimens remains largely empirical. This narrative review summarizes biomarkers with potential to inform first-line selection in metastatic PDAC, emphasizing [...] Read more.
Metastatic pancreatic ductal adenocarcinoma (PDAC) is typically treated with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel (GnP), but the choice between regimens remains largely empirical. This narrative review summarizes biomarkers with potential to inform first-line selection in metastatic PDAC, emphasizing genomic and transcriptomic correlates of differential benefit. Recent head-to-head trials, particularly Pancreatic Adenocarcinoma Signature Stratification for Treatment (PASS-01) and GENERATE (Japan Clinical Oncology Group [JCOG] 1611), indicate that modified FOLFIRINOX (mFOLFIRINOX) is not uniformly superior to GnP, strengthening the rationale for biomarker-guided selection. The strongest evidence favoring platinum-based/FOLFIRINOX strategies involves homologous recombination repair deficiency (HRD), especially alterations in germline breast cancer gene 1/2 (BRCA1/2) or partner and localizer of BRCA2 (PALB2), as well as broader genomic scar signatures. Transcriptomic subtype and GATA-binding protein 6 (GATA6) expression are promising but remain unsettled because retrospective data favor classical/GATA6-high disease for FOLFIRINOX, whereas PASS-01 suggested better outcomes with GnP in classical tumors. Candidate biomarkers favoring GnP include high human equilibrative nucleoside transporter 1 (hENT1), low class III β-tubulin (TUBB3) expression, and exploratory phosphatidylinositol 3-kinase (PI3K)/KIT/NOTCH pathway mutation signals. Comprehensive molecular profiling also identifies actionable alterations that may redirect patients to targeted therapy or clinical trials rather than standard chemotherapy alone. Importantly, no biomarker has yet been prospectively validated in a biomarker-stratified randomized trial with regimen selection as the primary endpoint; all biomarker-regimen associations described in this review should therefore be considered hypothesis-generating rather than practice-defining. Nevertheless, the convergence of genomic, transcriptomic, and organoid-based approaches makes biologically informed first-line selection increasingly feasible in metastatic PDAC. Full article
(This article belongs to the Special Issue Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors)
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31 pages, 631 KB  
Review
Pathogenesis, Diagnostic Pathways, and New Therapeutic and Nutritional Strategies for Pancreatic Cancer-Associated Cachexia
by Wiktoria Klus, Jagoda Ossowska, Katarzyna Kowalcze, Anna Kiliszczyk and Agnieszka Paziewska
Cancers 2026, 18(7), 1060; https://doi.org/10.3390/cancers18071060 - 25 Mar 2026
Cited by 1 | Viewed by 2441
Abstract
Background/Objectives: Pancreatic cancer-associated cachexia (CAC) is a complex, multifactorial and multi-organ metabolic syndrome affecting approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC). Recent epidemiological data show that cachexia is a primary cause of mortality in PDAC, directly accounting for approximately 30% [...] Read more.
Background/Objectives: Pancreatic cancer-associated cachexia (CAC) is a complex, multifactorial and multi-organ metabolic syndrome affecting approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC). Recent epidemiological data show that cachexia is a primary cause of mortality in PDAC, directly accounting for approximately 30% of cancer-related deaths and significantly limiting the tolerability of cancer therapy and is associated with adverse effects of treatment. It is defined by systemic weight loss, skeletal muscle atrophy (sarcopenia), and adipose tissue depletion, often driven by systemic inflammation and metabolic dysregulation. Methods: The literature was searched in PubMed and Scopus using combinations of keywords. The search covers the literature between 2016 and 2026, but papers before this period were also included because of their historical importance. Studies with higher evidential value, such as prospective studies, randomized controlled trials, and meta-analyses, were prioritized and emphasized in our analysis. Results: CAC in PC arises from a systemic inflammatory response driven by tumor–host interactions and the release of pro-inflammatory mediators, such as growth differentiation factor 15 (GDF-15) and parathyroid hormone-related protein (PTHrP), which promotes anorexia and weight loss. The most commonly used diagnostic criteria include unintentional weight loss of more than 5% of body mass within 6 months, a body mass index (BMI) below 20 kg/m2, or weight loss greater than 2% in the presence of sarcopenia. Emerging evidence supports the use of AI-based body composition analysis and novel biomarkers, including GDF-15 levels, to improve the detection and monitoring of cachexia. This review highlights that, despite the absence of pharmacological agents specifically approved for CAC in the United States and Europe, current guidelines recommend multimodal supportive care, including low-dose olanzapine, nutritional support, and exercise-based interventions. Furthermore, we identify recent phase 2 trials targeting the GDF-15 pathway, such as the GDF-15 inhibitor ponsegromab, which have demonstrated significant improvements in body weight and physical activity, suggesting a potential breakthrough in targeted therapies for CAC. Conclusions: CAC in PDAC represents a critical unmet medical need in oncology. It manifests as a lethal systemic pathology that demands early identification and targeted personalized pharmacological and nutritional interventions. Early diagnosis and targeted intervention represent promising strategies for improving survival and quality of life in this high-risk patient population. Full article
(This article belongs to the Special Issue Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors)
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22 pages, 747 KB  
Review
CA19-9 as a Dynamic Biomarker for Continuous Monitoring of Therapeutic Efficacy in Pancreatic Adenocarcinoma
by Luigi Brancato, Damar Osok, Laurent Van den Bossche, Eric Van Cutsem, Susan E. Bates, Johan Van den Bossche and Johannes Bogers
Cancers 2025, 17(24), 3902; https://doi.org/10.3390/cancers17243902 - 5 Dec 2025
Cited by 8 | Viewed by 6537
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to late-stage diagnosis and limited therapeutic efficacy. The carbohydrate antigen 19-9 (CA19-9) is the most widely used serum biomarker in the management of PDAC. While CA19-9 has significant limitations as [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to late-stage diagnosis and limited therapeutic efficacy. The carbohydrate antigen 19-9 (CA19-9) is the most widely used serum biomarker in the management of PDAC. While CA19-9 has significant limitations as a screening or diagnostic tool, including low sensitivity for early-stage disease and a lack of expression in the Lewis antigen-negative population, its value in the post-diagnostic setting is well established. This review examines the production and clearance dynamics of CA19-9. It critically evaluates how these factors impact its role as a biomarker for prognosis, assessment of resectability, and real-time monitoring of therapeutic response and recurrence in patients with PDAC. We explore how the relatively short half-life and correlation with tumor burden make CA19-9 a dynamic tool for tracking disease progression and treatment efficacy, often providing insights that precede radiographic changes. This review concludes that, despite its limitations, CA19-9 remains an important, cost-effective, and widely accessible biomarker for the longitudinal management of patients with established pancreatic cancer. Its dynamic changes allow continuous real-time disease monitoring providing critical information for clinical decision-making. Full article
(This article belongs to the Special Issue Advances in Pancreatic Cancer: Exploring Biomarkers and Prognostic Predictors)
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