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Updated: May 19, 2026
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
The pancreas cancer microenvironment
Christine Feig1, Aarthi Gopinathan, Albrecht Neesse
1Cambridge Research Institute, Cancer Research UK.
Abstract:
Pancreatic ductal adenocarcinoma (PDA) is a common and lethal malignancy resulting in more than 250,000 deaths per year worldwide. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with PDA to date. One contributing factor to the failure of systemic therapies may be the abundant tumor stromal content that is the characteristic of PDA. The PDA stroma, aptly termed the tumor microenvironment, occupies the majority of the tumor mass, and consists of a dynamic assortment of extracellular matrix components and nonneoplastic cells including fibroblastic, vascular, and immune cells. Recent work has revealed that the PDA stroma supports tumor growth and promotes metastasis and simultaneously serves as a physical barrier to drug delivery. Accordingly, methods that alter stromal composition or function, for instance interference with the vasculature via Notch/Hedgehog pathway inhibition or relief of vascular compression by hyaluronidase, are under active investigation. Here, we will review our current understanding of the PDA tumor microenvironment, and highlight opportunities for further exploration that may benefit patients.
Insights
Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer where therapies often fail due to its dense tumor microenvironment. Targeting this stroma offers new hope for improving treatment efficacy in pancreatic cancer patients.
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment Research
Background:
- Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy with poor therapeutic outcomes.
- Current cytotoxic and targeted therapies demonstrate limited efficacy in PDA patients.
- The abundant tumor stroma, or tumor microenvironment (TME), is a key characteristic of PDA.
Purpose of the Study:
- To review the current understanding of the pancreatic ductal adenocarcinoma tumor microenvironment.
- To highlight the role of the TME in supporting tumor growth, metastasis, and therapeutic resistance.
- To identify opportunities for therapeutic strategies targeting the PDA TME.
Main Methods:
- Review of existing literature on pancreatic ductal adenocarcinoma stroma and TME.
- Analysis of the composition and function of the PDA TME, including extracellular matrix and nonneoplastic cells.
- Discussion of therapeutic strategies targeting stromal components and pathways.
Main Results:
- The PDA stroma comprises the majority of the tumor mass, including extracellular matrix, fibroblastic, vascular, and immune cells.
- The TME supports tumor progression, metastasis, and acts as a physical barrier to drug delivery.
- Therapeutic approaches targeting the TME, such as Notch/Hedgehog pathway inhibition and hyaluronidase treatment, are under investigation.
Conclusions:
- The pancreatic ductal adenocarcinoma tumor microenvironment plays a critical role in disease progression and treatment failure.
- Modulating the TME presents a promising avenue for developing more effective therapies for PDA.
- Further exploration of TME-targeting strategies is crucial for improving patient outcomes in pancreatic cancer.
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