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Carcinogenesis. 2014 Jul;35(7):1451-60. doi: 10.1093/carcin/bgu115. Epub 2014 Jun 7.

Stromal reengineering to treat pancreas cancer.

Author information

1
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Department of Immunology, University of Washington, Seattle, WA 98195, USA.
2
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
3
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Department of Immunology, University of Washington, Seattle, WA 98195, USA, Department of Medicine, Division of Medical Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA and.
4
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Department of Medicine, Division of Medical Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA srh@fhcrc.org.

Abstract

Pancreatic ductal adenocarcinoma co-opts multiple cellular and extracellular mechanisms to create a complex cancer organ with an unusual proclivity for metastasis and resistance to therapy. Cell-autonomous events are essential for the initiation and maintenance of pancreatic ductal adenocarcinoma, but recent studies have implicated critical non-cell autonomous processes within the robust desmoplastic stroma that promote disease pathogenesis and resistance. Thus, non-malignant cells and associated factors are culprits in tumor growth, immunosuppression and invasion. However, even this increasing awareness of non-cell autonomous contributions to disease progression is tempered by the conflicting roles stromal elements can play. A greater understanding of stromal complexity and complicity has been aided in part by studies in highly faithful genetically engineered mouse models of pancreatic ductal adenocarcinoma. Insights gleaned from such studies are spurring the development of therapies designed to reengineer the pancreas cancer stroma and render it permissive to agents targeting cell-autonomous events or to reinstate immunosurveillance. Integrating conventional and immunological treatments in the context of stromal targeting may provide the key to a durable clinical impact on this formidable disease.

PMID:
24908682
PMCID:
PMC4076816
DOI:
10.1093/carcin/bgu115
[Indexed for MEDLINE]
Free PMC Article

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