Cited by 950Pancreatic and Hepatic Oncology ResearchPancreatitis Pathology and TreatmentCancer Cells and Metastasis

Pancreatic cancer stroma: an update on therapeutic targeting strategies

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Hosein, Abdel N., Brekken, Rolf A., Maitra, Anirban·2020·Nature Reviews Gastroenterology & Hepatology

Abstract

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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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
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
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

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