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Emerging concepts in pancreatic cancer medicine: targeting the tumor stroma

Authors Neesse A, Krug S, Gress TM, Tuveson DA, Michl P

Received 24 September 2013

Accepted for publication 2 November 2013

Published 18 December 2013 Volume 2014:7 Pages 33—43

DOI https://doi.org/10.2147/OTT.S38111

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Albrecht Neesse,1 Sebastian Krug,1 Thomas M Gress,1 David A Tuveson,2 Patrick Michl1

1Department of Gastroenterology, Endocrinology, Infectiology and Metabolism, Philipps University Marburg, Marburg, Germany; 2Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA

Abstract: Pancreatic ductal adenocarcinoma is a stroma-rich and highly challenging cancer to treat. Over recent years, it has become increasingly evident that the complex network of soluble cytokines, growth factors, proteases, and components of the extracellular matrix collaboratively interact within the tumor microenvironment, sustaining and driving cancer cell proliferation, invasion, and early metastasis. More recently, the tumor microenvironment has also been appreciated to mediate therapeutic resistance in pancreatic ductal adenocarcinoma, thus opening numerous avenues for novel therapeutic explorations. Inert and soluble components of the tumor stroma have been targeted in order to break down the extracellular matrix scaffold, relieve vessel compression, and increase drug delivery to hypovascular tumors. Moreover, targeting of antiapoptotic, immunosuppressive, and pro-proliferative effects of the tumor stroma provides novel vantage points of attack. This review focuses on current and future developments in pancreatic cancer medicine, with a particular emphasis on biophysical and biochemical approaches that target the tumor microenvironment.

Keywords: pancreatic cancer, chemoresistance, tumor stroma, drug delivery

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