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Biomedicines
Special Issues
Pancreatic Cancer Heterogeneity and Therapeutic Implications
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Pancreatic Cancer Heterogeneity and Therapeutic Implications

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

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 7602

Special Issue Editor

Dr. Tatjana Arsenijevic

E-Mail Website
Guest Editor
1. Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium
2. Department of Gastroenterology, Hepatology and Digestive Oncology, Hopital Universitaire de Bruxelles H.U.B. CUB Hopital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium
Interests: pancreatic cancer research; tumoral heterogeneity, resistance to therapy; precision medicine in PDAC

Special Issue Information

Dear Colleagues,

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive cancer with an abysmal prognosis and a 5-year overall survival of 9%. The only potential cure is surgery, but few patients present with resectable tumors at the time of diagnosis, which is often delayed by the vagueness of symptoms and the lack of specific clinical markers for early stages of PDAC. PDAC is also among the most chemoresistant cancers. Major obstacles to the effective treatment of patients with pancreatic cancer are its high heterogeneity translated in a diverse pattern of clinical outcomes and responses to therapies. There is a remarkably high histological heterogeneity between the PDAC tumors (intertumoral heterogeneity), but also within a single tumor (intratumoral heterogeneity). Deep molecular profiling of pancreatic tumors confirmed high PDAC intertumoral and intratumoral heterogeneity and distinguished several subtypes at the genomic, transcriptomic and metabolomics levels that are instructive in predicting prognosis and sensitivity to treatment. 

Another key characteristic of pancreatic cancer is that PDAC stroma exhibits a strong desmoplastic feature, with stromal components often outnumbering cancer cells. The role of the stroma in PDAC is complex, with at least some stromal constituents acting to restrain rather than promote tumor progression, calling for a further comprehensive characterization of tumor–stroma crosstalk.

In this Special Issue, we welcome original and review papers that focus on the recent advances in the field of pancreatic cancer research, covering but not limited to (1) molecular insights of PDAC heterogeneity, (2) molecular mechanisms of innate and acquired resistance to therapy (3) characterization of tumor-stroma crosstalk and (4) potential novel targeted therapies. 

We look forward to receiving your contributions.

Dr. Tatjana Arsenijevic
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 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 tumoral heterogeneity
  • PDAC molecular subtypes
  • resistance to therapy
  • precision medicine in PDAC
  • new therapeutic combinations for PDAC subtypes

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Published Papers (3 papers)

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Review

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28 pages, 1205 KiB  
Review
Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging
by Rita Saúde-Conde, Ayça Arçay Öztürk, Kosta Stosic, Oier Azurmendi Senar, Julie Navez, Christelle Bouchart, Tatjana Arsenijevic, Patrick Flamen and Jean-Luc Van Laethem
Biomedicines 2024, 12(3), 591; https://doi.org/10.3390/biomedicines12030591 - 6 Mar 2024
Cited by 7 | Viewed by 3516
Abstract
Pancreatic ductal adenocarcinoma (PDAC) represents a formidable challenge due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) in PDAC, characterized by intense stromal desmoplastic reactions and a dominant presence of cancer-associated fibroblasts (CAFs), significantly contributes to therapeutic resistance. However, within [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) represents a formidable challenge due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) in PDAC, characterized by intense stromal desmoplastic reactions and a dominant presence of cancer-associated fibroblasts (CAFs), significantly contributes to therapeutic resistance. However, within the heterogeneous CAF population, fibroblast activation protein (FAP) emerges as a promising target for Gallium-68 FAP inhibitor positron emission tomography (Ga68FAPI-PET) imaging. Notably, 68Ga-FAPI-PET demonstrates promising diagnostic sensitivity and specificity, especially in conjunction with low tracer uptake in non-tumoral tissues. Moreover, it provides valuable insights into tumor–stroma interactions, a critical aspect of PDAC tumorigenesis not adequately visualized through conventional methods. The clinical implications of this innovative imaging modality extend to its potential to reshape treatment strategies by offering a deeper understanding of the dynamic TME. However, while the potential of 68Ga-FAPI-PET is evident, ongoing correlative studies are essential to elucidate the full spectrum of CAF heterogeneity and to validate its impact on PDAC management. This article provides a comprehensive review of CAF heterogeneity in PDAC and explores the potential impact of 68Ga-FAPI-PET on disease management. Full article
(This article belongs to the Special Issue Pancreatic Cancer Heterogeneity and Therapeutic Implications)
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11 pages, 3619 KiB  
Systematic Review
Accuracy of the END-PAC Model in Predicting the Risk of Developing Pancreatic Cancer in Patients with New-Onset Diabetes: A Systematic Review and Meta-Analysis
by Shahab Hajibandeh, Christina Intrator, Eliot Carrington-Windo, Rhodri James, Ioan Hughes, Shahin Hajibandeh and Thomas Satyadas
Biomedicines 2023, 11(11), 3040; https://doi.org/10.3390/biomedicines11113040 - 14 Nov 2023
Cited by 3 | Viewed by 1953
Abstract
Objectives: To investigate the performance of the END-PAC model in predicting pancreatic cancer risk in individuals with new-onset diabetes (NOD). Methods: The PRISMA statement standards were followed to conduct a systematic review. All studies investigating the performance of the END-PAC model in predicting [...] Read more.
Objectives: To investigate the performance of the END-PAC model in predicting pancreatic cancer risk in individuals with new-onset diabetes (NOD). Methods: The PRISMA statement standards were followed to conduct a systematic review. All studies investigating the performance of the END-PAC model in predicting pancreatic cancer risk in individuals with NOD were included. Two-by-two tables, coupled forest plots and summary receiver operating characteristic plots were constructed using the number of true positives, false negatives, true negatives and false positives. Diagnostic random effects models were used to estimate summary sensitivity and specificity points. Results: A total of 26,752 individuals from four studies were included. The median follow-up was 3 years and the pooled risk of pancreatic cancer was 0.8% (95% CI 0.6–1.0%). END-PAC score ≥ 3, which classifies the patients as high risk, was associated with better predictive performance (sensitivity: 55.8% (43.9–67%); specificity: 82.0% (76.4–86.5%)) in comparison with END-PAC score 1–2 (sensitivity: 22.2% (16.6–29.2%); specificity: 69.9% (67.3–72.4%)) and END-PAC score < 1 (sensitivity: 18.0% (12.8–24.6%); specificity: 50.9% (48.6–53.2%)) which classify the patients as intermediate and low risk, respectively. The evidence quality was judged to be moderate to high. Conclusions: END-PAC is a promising model for predicting pancreatic cancer risk in individuals with NOD. The score ≥3 should be considered as optimum cut-off value. More studies are needed to assess whether it could improve early pancreatic cancer detection rate, pancreatic cancer re-section rate, and pancreatic cancer treatment outcomes. Full article
(This article belongs to the Special Issue Pancreatic Cancer Heterogeneity and Therapeutic Implications)
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15 pages, 592 KiB  
Systematic Review
Preoperative C-Reactive Protein-to-Albumin Ratio and Its Ability to Predict Outcomes of Pancreatic Cancer Resection: A Systematic Review
by Shahin Hajibandeh, Shahab Hajibandeh, Saleh Romman, Alessandro Parente, Richard W. Laing, Thomas Satyadas, Daren Subar, Somaiah Aroori, Anand Bhatt, Damien Durkin, Tejinderjit S. Athwal and Keith J. Roberts
Biomedicines 2023, 11(7), 1983; https://doi.org/10.3390/biomedicines11071983 - 13 Jul 2023
Cited by 5 | Viewed by 1632
Abstract
Objectives. To evaluate the ability of the c-reactive protein-to-albumin ratio (CAR) in predicting outcomes in patients undergoing pancreatic cancer resection. Methods. A systematic search of electronic information sources and bibliographic reference lists was conducted. Survival outcomes and perioperative morbidity were the evaluated outcome [...] Read more.
Objectives. To evaluate the ability of the c-reactive protein-to-albumin ratio (CAR) in predicting outcomes in patients undergoing pancreatic cancer resection. Methods. A systematic search of electronic information sources and bibliographic reference lists was conducted. Survival outcomes and perioperative morbidity were the evaluated outcome parameters. Results. Eight studies reporting a total of 1056 patients undergoing pancreatic cancer resection were identified. The median cut-off value for CAR was 0.05 (range 0.0003–0.54). Using multivariate analysis, all studies demonstrated that a higher CAR value was an independent and significant predictor of poor overall survival in patients undergoing pancreatic cancer resection. The estimated hazard ratio (HR) ranged from 1.4 to 3.6. Although there was a positive correlation between the reported cut-off values for CAR and HRs for overall survival, it was weak and non-significant (r = 0.36, n = 6, p = 0.480). There was significant between-study heterogeneity. Conclusions. Preoperative CAR value seems to be an important prognostic score in predicting survival outcomes in patients undergoing pancreatic cancer resection. However, the current evidence does not allow the determination of an optimal cut-off value for CAR, considering the heterogeneous reporting of cut-off values by the available studies and the lack of knowledge of their sensitivity and specificity. Future research is required. Full article
(This article belongs to the Special Issue Pancreatic Cancer Heterogeneity and Therapeutic Implications)
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