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Intervention on toll-like receptors in pancreatic cancer

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Author

Summary, in English

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.

Department/s

  • Surgery (Lund)
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2014

Language

English

Pages

5808-5817

Publication/Series

World Journal of Gastroenterology

Volume

20

Issue

19

Document type

Journal article review

Publisher

WJG Press

Topic

  • Gastroenterology and Hepatology

Keywords

  • Adjuvant therapy
  • Intervention
  • Pancreatic cancer
  • Pathophysiological mechanism
  • Toll-like receptor

Status

Published

ISBN/ISSN/Other

  • ISSN: 1007-9327