Stromal re-engineering to treat pancreas cancer.

Publication Type:

Journal Article

Source:

Carcinogenesis, Volume 35, Issue 7, p.1451-60 (2014)

Keywords:

2014, Center-Authored Paper, Clinical Research Division, June 2014, Public Health Sciences Division

Abstract:

Pancreatic ductal adenocarcinoma (PDA) co-opts cellular 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 PDA, but non-malignant cells and associated factors are also culprits in tumor growth, immunosuppression, and invasion. Recent studies have implicated critical non-cell autonomous processes within the robust desmoplastic stroma that promote disease pathogenesis and resistance. A greater understanding of the stromal content and complexity has been aided in part by studies in highly faithful genetically engineered mouse models of PDA. Insights gleaned from such studies are spurring the development of therapies designed to re-engineer 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.