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World J Gastroenterol. Mar 7, 2014; 20(9): 2237-2246
Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2237
Pancreatic cancer stroma: Understanding biology leads to new therapeutic strategies
Agnieszka Anna Rucki, Lei Zheng
Agnieszka Anna Rucki, Lei Zheng, Department of Oncology, The Sidney Kimmel Cancer Center, the Skip Viragh Clinical Pancreatic Cancer Center, and the Sol Goldman Pancreatic Cancer Center, Johns Hopkins University, Baltimore, MD 21287, United States
Author contributions: Rucki AA wrote the manuscript; and Zheng L developed the concept and revised the manuscript.
Supported by NIH R01 CA169702-01A1 (to Zheng L); NIH K23 CA148964-01 (to Zheng L); Johns Hopkins School of Medicine Clinical Scientist Award (to Zheng L); Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins (to Zheng L); The National Pancreas Foundation (to Zheng L); Lefkofsky Family Foundation (to Zheng L); the NCI SPORE in Gastrointestinal Cancers P50 CA062924 (to Zheng L); Lustgarten Foundation (to Zheng L); and the Sol Goldman Pancreatic Cancer Center grants (to Zheng L)
Correspondence to: Lei Zheng, MD, PhD, Department of Oncology, The Sidney Kimmel Cancer Center, the Skip Viragh Clinical Pancreatic Cancer Center, and the Sol Goldman Pancreatic Cancer Center, Johns Hopkins University, 1650 Orleans Street, CRB1 Room 488, Baltimore, MD 21287, United States. lzheng6@jhmi.edu
Telephone: +1-410-5026241 Fax: +1-410-4168216
Received: October 22, 2013
Revised: December 14, 2013
Accepted: January 19, 2014
Published online: March 7, 2014
Processing time: 135 Days and 6.5 Hours
Abstract

Pancreatic ductal adenocarcinoma (PDA) is among the deadliest cancers in the United States and in the world. Late diagnosis, early metastasis and lack of effective therapy are among the reasons why only 6% of patients diagnosed with PDA survive past 5 years. Despite development of targeted therapy against other cancers, little progression has been made in the treatment of PDA. Therefore, there is an urgent need for the development of new treatments. However, in order to proceed with treatments, the complicated biology of PDA needs to be understood first. Interestingly, majority of the tumor volume is not made of malignant epithelial cells but of stroma. In recent years, it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells, leading to cancer progression. The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery. Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery. In this review, we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.

Keywords: Pancreatic ductal adenocarcinoma; Stroma; Tumor microenvironment; Pancreatic stellate cells; Cancer associated fibroblast; Sonic hedgehog; Hepatic growth factor; Fibroblast activation protein

Core tip: This is a comprehensive review and an update on recent progresses in understanding the role of tumor microenvironment in the growth, invasion and metastasis of pancreatic cancer. The role of tumor microenvironment in anti-tumor immune response and treatment of pancreatic cancer is also reviewed. How our knowledge in tumor microenvironment is translated into the development of pancreatic cancer therapy is discussed.