Intervention on toll-like receptors in pancreatic cancer

Research output: Contribution to journalReview article

Standard

Intervention on toll-like receptors in pancreatic cancer. / Vaz, Juan; Andersson, Roland.

In: World Journal of Gastroenterology, Vol. 20, No. 19, 2014, p. 5808-5817.

Research output: Contribution to journalReview article

Harvard

APA

CBE

MLA

Vancouver

Author

RIS

TY - JOUR

T1 - Intervention on toll-like receptors in pancreatic cancer

AU - Vaz, Juan

AU - Andersson, Roland

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Adjuvant therapy

KW - Intervention

KW - Pancreatic cancer

KW - Pathophysiological mechanism

KW - Toll-like receptor

U2 - 10.3748/wjg.v20.i19.5808

DO - 10.3748/wjg.v20.i19.5808

M3 - Review article

VL - 20

SP - 5808

EP - 5817

JO - World Journal of Gastroenterology

T2 - World Journal of Gastroenterology

JF - World Journal of Gastroenterology

SN - 1007-9327

IS - 19

ER -