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 |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:cmedm&genre=article&issn=20734409&ISBN=&volume=15&issue=18&date=20260910&spage=&pages=&title=Cells&atitle=Biomarker-Driven%20Strategies%20for%20Stromal%20Reprogramming%20in%20Pancreatic%20Ductal%20Adenocarcinoma.&aulast=De%20Luca%20M&id=DOI:10.3390/cells15181637 Name: Full Text Finder (for New FTF UI) (ns324271) Category: fullText Text: Full Text Finder MouseOverText: Full Text Finder |
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| Header | DbId: cmedm DbLabel: MEDLINE An: 42782738 AccessLevel: 3 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AU" term="%22De+Luca+M%22">De Luca M</searchLink>; Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy.<br /><searchLink fieldCode="AU" term="%22Balestra+F%22">Balestra F</searchLink>; Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy.<br /><searchLink fieldCode="AU" term="%22Panzetta+G%22">Panzetta G</searchLink>; Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy.<br /><searchLink fieldCode="AU" term="%22Giannelli+G%22">Giannelli G</searchLink>; Scientific Direction, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy.<br /><searchLink fieldCode="AU" term="%22Scavo+MP%22">Scavo MP</searchLink>; Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS de Bellis, Via Turi 27, Castellana Grotte, 70013 Bari, Italy. – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22101600052%22">Cells</searchLink> [Cells] 2026 Sep 10; Vol. 15 (18). <i>Date of Electronic Publication: </i>2026 Sep 10. – Name: TypePub Label: Publication Type Group: TypPub Data: Journal Article; Review – Name: Language Label: Language Group: Lang Data: English – Name: TitleSource Label: Journal Info Group: Src Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22MDPI%22">MDPI </searchLink><i>Country of Publication: </i>Switzerland <i>NLM ID: </i>101600052 <i>Publication Model: </i>Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>2073-4409 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2220734409%22">20734409 </searchLink><i>NLM ISO Abbreviation: </i>Cells <i>Subsets: </i>MEDLINE – Name: PublisherInfo Label: Imprint Name(s) Group: PubInfo Data: <i>Original Publication</i>: Basel, Switzerland : MDPI – Name: SubjectMESH Label: MeSH Terms Group: Su Data: <searchLink fieldCode="MM" term="%22Carcinoma%2C+Pancreatic+Ductal%22">Carcinoma, Pancreatic Ductal*</searchLink>/<searchLink fieldCode="MM" term="%22Carcinoma%2C+Pancreatic+Ductal+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Carcinoma%2C+Pancreatic+Ductal%22">Carcinoma, Pancreatic Ductal*</searchLink>/<searchLink fieldCode="MM" term="%22Carcinoma%2C+Pancreatic+Ductal+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Biomarkers%2C+Tumor%22">Biomarkers, Tumor*</searchLink>/<searchLink fieldCode="MM" term="%22Biomarkers%2C+Tumor+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Pancreatic+Neoplasms%22">Pancreatic Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Pancreatic+Neoplasms+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Pancreatic+Neoplasms%22">Pancreatic Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Pancreatic+Neoplasms+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Stromal+Cells%22">Stromal Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Stromal+Cells+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Stromal+Cells%22">Stromal Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Stromal+Cells+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Cellular+Reprogramming%22">Cellular Reprogramming*</searchLink><br /><searchLink fieldCode="MH" term="%22Extracellular+Matrix%22">Extracellular Matrix</searchLink>/<searchLink fieldCode="MH" term="%22Extracellular+Matrix+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Cancer-Associated+Fibroblasts%22">Cancer-Associated Fibroblasts</searchLink>/<searchLink fieldCode="MH" term="%22Cancer-Associated+Fibroblasts+pathology%22">pathology</searchLink> ; <searchLink fieldCode="MH" term="%22Cancer-Associated+Fibroblasts%22">Cancer-Associated Fibroblasts</searchLink>/<searchLink fieldCode="MH" term="%22Cancer-Associated+Fibroblasts+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Tumor+Microenvironment%22">Tumor Microenvironment</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 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. – Name: Ref Label: References Group: RefInfo Data: Cancers (Basel). 2021 Nov 17;13(22):. (PMID: <searchLink fieldCode="PM" term="%2234830914%22">34830914)</searchLink><br />Biomed Pharmacother. 2026 Jan;194:118892. (PMID: <searchLink fieldCode="PM" term="%2241389627%22">41389627)</searchLink><br />Int J Surg. 2025 Jan 01;111(1):950-961. (PMID: <searchLink fieldCode="PM" term="%2239172712%22">39172712)</searchLink><br />BMC Cancer. 2025 Jul 24;25(1):1209. (PMID: <searchLink fieldCode="PM" term="%2240707920%22">40707920)</searchLink><br />ACS Nano. 2024 Oct 22;18(42):28502-28530. (PMID: <searchLink fieldCode="PM" term="%2239377250%22">39377250)</searchLink><br />Oncologist. 2025 Jan 17;30(1):. 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(PMID: <searchLink fieldCode="PM" term="%2232442601%22">32442601)</searchLink> – Name: GrantInfo Label: Grant Information Group: Grant Data: Ricerca Corrente 2026 Ministero della Salute – Name: SubjectMinor Label: Contributed Indexing Group: Data: <i>Keywords: </i>biomarkers; cancer-associated fibroblasts; extracellular matrix; pancreatic ductal adenocarcinoma; stromal reprogramming; tumor microenvironment – Name: NumberCAS Label: Substance Nomenclature Group: ID Data: 0 (Biomarkers, Tumor) – Name: DateEntry Label: Entry Date(s) Group: Date Data: <i>Date Created: </i>20260924 <i>Date Completed: </i>20260924 <i>Latest Revision: </i>20260926 – Name: DateUpdate Label: Update Code Group: Date Data: 20260926 – Name: PubmedCentralID Label: PubMed Central ID Group: ID Data: PMC13605378 – Name: DOI Label: DOI Group: ID Data: 10.3390/cells15181637 – Name: AN Label: PMID Group: ID Data: 42782738 |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42782738 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3390/cells15181637 Languages: – Code: eng Text: English Subjects: – SubjectFull: Extracellular Matrix metabolism Type: general – SubjectFull: Cancer-Associated Fibroblasts pathology Type: general – SubjectFull: Cancer-Associated Fibroblasts metabolism Type: general – SubjectFull: Humans Type: general – SubjectFull: Tumor Microenvironment Type: general – SubjectFull: Animals Type: general – SubjectFull: Carcinoma, Pancreatic Ductal pathology Type: general – SubjectFull: Carcinoma, Pancreatic Ductal metabolism Type: general – SubjectFull: Biomarkers, Tumor metabolism Type: general – SubjectFull: Pancreatic Neoplasms pathology Type: general – SubjectFull: Pancreatic Neoplasms metabolism Type: general – SubjectFull: Stromal Cells metabolism Type: general – SubjectFull: Stromal Cells pathology Type: general – SubjectFull: Cellular Reprogramming Type: general Titles: – TitleFull: Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: De Luca M – PersonEntity: Name: NameFull: Balestra F – PersonEntity: Name: NameFull: Panzetta G – PersonEntity: Name: NameFull: Giannelli G – PersonEntity: Name: NameFull: Scavo MP IsPartOfRelationships: – BibEntity: Dates: – D: 10 M: 09 Text: 2026 Sep 10 Type: published Y: 2026 Identifiers: – Type: issn-electronic Value: 2073-4409 Numbering: – Type: volume Value: 15 – Type: issue Value: 18 Titles: – TitleFull: Cells Type: main |
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