Pancreatic cancer stroma: an update on therapeutic targeting strategies
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality in the Western world with limited therapeutic options and dismal long-term survival. The neoplastic epithelium exists within a dense stroma, which is recognized as a critical mediator of disease progression through direct effects on cancer cells and indirect effects on the tumour immune microenvironment. The three dominant entities in the PDAC stroma are extracellular matrix (ECM), vasculature and cancer-associated fibroblasts (CAFs). The ECM can function as a barrier to effective drug delivery to PDAC cancer cells, and a multitude of strategies to target the ECM have been attempted in the past decade. The tumour vasculature is a complex system and, although multiple anti-angiogenesis agents have already failed late-stage clinical trials in PDAC, other vasculature-targeting approaches aimed at vessel normalization and tumour immunosensitization have shown promise in preclinical models. Lastly, PDAC CAFs participate in active cross-talk with cancer cells within the tumour microenvironment. The existence of intratumoural CAF heterogeneity represents a paradigm shift in PDAC CAF biology, with myofibroblastic and inflammatory CAF subtypes that likely make distinct contributions to PDAC progression. In this Review, we discuss our current understanding of the three principal constituents of PDAC stroma, their effect on the prevalent immune landscape and promising therapeutic targets within this compartment.
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The majority of collagen in PDAC is type I collagen, largely generated by CAFs.
“The majority of collagen is type I collagen164, largely generated by CAFs147,165”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [164]
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Pancreatic cancer: Advances and challenges
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- Authors
- Hosein, A. N., Brekken, R. A., & Maitra, A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Brekken, Rolf A.
- Maitra, Anirban
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2020-05-11
- Volume
- 17
- Issue
- 8
- Pages
- 487-505
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC8284850
- OpenAlex
- W3023906975
- Cited by
- 950
- References
- 193
- Citations by year
- 2026: 134 · 2025: 187 · 2024: 174 · 2023: 155 · 2022: 165 · 2021: 121 · 2020: 14
- FWCI
- 12.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U54CA210181, R01CA220236, U01CA252965, U24CA224020, R01CA192381, R01CA218004)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- pancreatic ductal adenocarcinoma, tumor stroma, extracellular matrix, tumor vasculature, cancer-associated fibroblasts, anti-angiogenic therapy, vessel normalization, tumor immune microenvironment, drug delivery barriers, CAF heterogeneity, myofibroblastic CAFs, inflammatory CAFs, therapeutic targeting
- MeSH terms
- Cancer-Associated Fibroblasts, Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Benzamides, Extracellular Matrix, Humans, Hyaluronic Acid, Hyaluronoglucosaminidase, Pancreatic Neoplasms, Permeability, Pressure, Pyrazines, Sulfonamides, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Angiogenesis Inhibitors, Carcinoma, Pancreatic Ductal, Extracellular Fluid, Protein Kinase Inhibitors, Mice, Focal Adhesion Protein-Tyrosine Kinases, rho-Associated Kinases, Molecular Targeted Therapy, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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