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Updated: May 5, 2026
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
Published on: June 20, 2015
Stromal biology and therapy in pancreatic cancer
Albrecht Neesse1, Patrick Michl, Kristopher K Frese
1Li Ka Shing Centre, Cambridge Research Institute, Cancer Research UK, Cambridge, UK.
Abstract:
Pancreatic ductal adenocarcinoma (PDA) is an almost uniformly lethal disease. One explanation for the devastating prognosis is the failure of many chemotherapies, including the current standard of care therapy gemcitabine. Although our knowledge of the molecular events underlying multistep carcinogenesis in PDA has steadily increased, translation into more effective therapeutic approaches has been inefficient over the last several decades. Evidence for this innate resistance to systemic therapies was recently provided in an accurate mouse model of PDA by the demonstration that chemotherapies are poorly delivered to PDA tissues because of a deficient vasculature. This vascular deficiency correlated with the presence of a dense stromal matrix that is a prominent histological hallmark of PDA tumours. Therapeutic targeting of stromal cells decreased the stroma from pancreatic tumours, resulting in increased intratumoral perfusion and therapeutic delivery of gemcitabine. Stromal cells contained within the PDA tumour microenvironment therefore represent an additional constituent to neoplastic cells that should be critically evaluated for optimal therapeutic development in preclinical models and early clinical trials.
Insights
Pancreatic ductal adenocarcinoma (PDA) treatment fails due to poor drug delivery, caused by deficient tumor vasculature and dense stroma. Targeting stromal cells improved drug delivery and therapeutic efficacy in a PDA mouse model.
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment Research
Background:
- Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, with limited success of current chemotherapies like gemcitabine.
- Multistep carcinogenesis in PDA is well-studied, but therapeutic advancements remain inefficient.
- Innate resistance to systemic therapies in PDA is linked to poor drug delivery.
Purpose of the Study:
- To investigate the role of tumor vasculature and stroma in PDA chemotherapy resistance.
- To evaluate the therapeutic potential of targeting stromal cells in PDA.
Main Methods:
- Utilized an accurate mouse model of PDA.
- Assessed chemotherapy delivery to PDA tissues.
- Investigated the correlation between vascular deficiency, stromal matrix density, and drug delivery.
- Evaluated the effect of therapeutic targeting of stromal cells.
Main Results:
- Chemotherapies exhibit poor delivery to PDA tissues due to deficient vasculature.
- Vascular deficiency in PDA is associated with a dense stromal matrix.
- Targeting stromal cells reduced tumor stroma, enhancing intratumoral perfusion.
- Improved perfusion led to increased delivery of gemcitabine.
Conclusions:
- Stromal cells within the PDA tumor microenvironment are critical targets for improving therapeutic efficacy.
- Therapeutic strategies should consider stromal cells alongside neoplastic cells for optimal PDA treatment development.
- Targeting the stroma shows promise for enhancing chemotherapy delivery and outcomes in preclinical PDA models and early clinical trials.
