Review
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World J Gastroenterol. May 21, 2014; 20(19): 5808-5817
Published online May 21, 2014. doi: 10.3748/wjg.v20.i19.5808
Intervention on toll-like receptors in pancreatic cancer
Juan Vaz, Roland Andersson
Juan Vaz, Roland Andersson, Department of Surgery, Clinical Sciences Lund, Skåne University Hospital Lund, Lund University, SE-221 85 Lund, Sweden
Author contributions: Vaz J collected the underlying material and wrote the initial draft of the manuscript; Andersson R and Vaz J designed the outline of the paper; Andersson R finalized and revised the manuscript; both authors have read and approved this final version.
Correspondence to: Roland Andersson, MD, PhD, Department of Surgery, Clinical Sciences Lund, Skåne University Hospital Lund, Lund University, SE-221 85 Lund, Sweden. roland.andersson@med.lu.se
Telephone: +46-461-72359 Fax: +46-461-72335
Received: November 8, 2013
Revised: February 19, 2014
Accepted: March 19, 2014
Published online: May 21, 2014
Abstract

Pancreatic ductal adenocarcinoma (PDA) is a devastating disease with pronounced morbidity and a high mortality rate. Currently available treatments lack convincing cost-efficiency determinations and are in most cases not associated with relevant success rate. Experimental stimulation of the immune system in murine PDA models has revealed some promising results. Toll-like receptors (TLRs) are pillars of the immune system that have been linked to several forms of malignancy, including lung, breast and colon cancer. In humans, TLRs are expressed in the pancreatic cancer tissue and in several cancer cell lines, whereas they are not expressed in the normal pancreas. In the present review, we explore the current knowledge concerning the role of different TLRs associated to PDA. Even if almost all known TLRs are expressed in the pancreatic cancer microenvironment, there are only five TLRs suggested as possible therapeutic targets. Most data points at TLR2 and TLR9 as effective tumor markers and agonists could potentially be used as e.g. future adjuvant therapies. The elucidation of the role of TLR3 in PDA is only in its initial phase. The inhibition/blockage of TLR4-related pathways has shown some promising effects, but there are still many steps left before TLR4 inhibitors can be considered as possible therapeutic agents. Finally, TLR7 antagonists seem to be potential candidates for therapy. Independent of their potential in immunotherapies, all existing data indicate that TLRs are strongly involved in the pathophysiology and development of PDA.

Keywords: Pancreatic cancer, Pathophysiological mechanism, Toll-like receptor, Intervention, Adjuvant therapy

Core tip: The combination of high mortality rates and a tremendously complex pathophysiology makes pancreatic ductal adenocarcinoma (PDA) an enormous challenge. We summarize the current knowledge about the importance of toll-like receptors (TLR) in PDA. Since both tumor and tumor-related cells express TLRs, intervention on TLR-related pathways may represent future candidates for therapy.