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Stromal biology and therapy in pancreatic cancer
  1. Albrecht Neesse1,
  2. Patrick Michl2,
  3. Kristopher K Frese1,
  4. Christine Feig1,
  5. Natalie Cook1,
  6. Mike A Jacobetz1,
  7. Martijn P Lolkema1,
  8. Malte Buchholz2,
  9. Kenneth P Olive3,
  10. Thomas M Gress2,
  11. David A Tuveson1
  1. 1Li Ka Shing Centre, Cambridge Research Institute, Cancer Research UK, Cambridge, UK
  2. 2Department of Gastroenterology, Endocrinology and Metabolism, Philipps-University, Marburg, Germany
  3. 3Department of Medicine, Dept. of Pathology, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA
  1. Correspondence to Dr David Tuveson, Li Ka Shing Centre, Cambridge Research Institute, Cancer Research UK, Robinson Way, Cambridge CB2 0RE, UK; david.tuveson{at}cancer.org.uk Prof Thomas Gress, Division of Gastroenterology, Endocrinology and Metabolism, University Hospital Giessen and Marburg, Campus Marburg Philipps University, Marburg, Baldinger Strasse, 35043 Marburg, Germany; gress{at}med.uni-marburg.de

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.

  • Pancreatic cancer
  • tumour microenvironment
  • tumour-stroma interactions
  • genetically engineered mouse models of pancreatic cancer
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Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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