Academic Journal
Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma.
| Title: | Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma. |
|---|---|
| Authors: | De Luca M; Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy., Balestra F; Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy., Panzetta G; Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy., Giannelli G; Scientific Direction, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy., Scavo MP; Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy. |
| Source: | Cells [Cells] 2026 Sep 10; Vol. 15 (18). Date of Electronic Publication: 2026 Sep 10. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI |
| MeSH Terms: | Carcinoma, Pancreatic Ductal*/pathology , Carcinoma, Pancreatic Ductal*/metabolism , Biomarkers, Tumor*/metabolism , Pancreatic Neoplasms*/pathology , Pancreatic Neoplasms*/metabolism , Stromal Cells*/metabolism , Stromal Cells*/pathology , Cellular Reprogramming*, Extracellular Matrix/metabolism ; Cancer-Associated Fibroblasts/pathology ; Cancer-Associated Fibroblasts/metabolism ; Humans ; Tumor Microenvironment ; Animals |
| Abstract: | Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, partly because its dense, heterogeneous stroma restricts drug delivery, promotes immune exclusion, and supports therapeutic resistance. Stromal targeting has, therefore, evolved from broad depletion towards biomarker-guided reprogramming and normalization strategies that aim to restore vascular function, improve intratumoral drug penetration, and enhance antitumor immunity. This review summarizes evidence on stromal biomarkers with prognostic or predictive value, including tumor-stroma ratio, fibrosis burden, cancer-associated fibroblast states, extracellular matrix stiffness, vascular accessibility, and spatial immune features. It also examines emerging therapeutic approaches to reprogram the PDAC stroma, such as repurposed drugs, immune-stromal modulators, metabolic interventions, and advanced delivery systems. Emphasis is placed on clinically or translationally supported strategies, including CXCR4, CD40, CD73, vitamin D receptor agonism, matrix remodeling, and biomarker-driven stratification. Overall, PDAC stroma is a dynamic therapeutic target, requiring composite biomarkers and rational combinations with chemotherapy, immunotherapy, and delivery-enhancing strategies. |
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| Grant Information: | Ricerca Corrente 2026 Ministero della Salute |
| Contributed Indexing: | Keywords: biomarkers; cancer-associated fibroblasts; extracellular matrix; pancreatic ductal adenocarcinoma; stromal reprogramming; tumor microenvironment |
| Substance Nomenclature: | 0 (Biomarkers, Tumor) |
| Entry Date(s): | Date Created: 20260924 Date Completed: 20260924 Latest Revision: 20260926 |
| Update Code: | 20260926 |
| PubMed Central ID: | PMC13605378 |
| DOI: | 10.3390/cells15181637 |
| PMID: | 42782738 |
| Database: | MEDLINE |
| ISSN: | 2073-4409 |
|---|---|
| DOI: | 10.3390/cells15181637 |