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Cancers 2015, 7(3), 1215-1232; doi:10.3390/cancers7030832

Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: a New Therapeutic Approach

1
Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital,41013 Sevilla, Spain
2
Laboratory of Neuroanatomy of the Peptidergic System (Lab. 14), Institute of Neurosciences ofCastilla y León (INCYL), University of Salamanca, 37008 Salamanca, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Hildegard M. Schuller
Received: 19 May 2015 / Revised: 27 June 2015 / Accepted: 30 June 2015 / Published: 6 July 2015
View Full-Text   |   Download PDF [363 KB, uploaded 6 July 2015]   |  

Abstract

Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase), the peptide substance P (SP)—at high concentrations—is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert An antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC. View Full-Text
Keywords: substance P; NK-1 receptor antagonist; chronic pancreatitis; inflammation; smoking; alcoholism; depression substance P; NK-1 receptor antagonist; chronic pancreatitis; inflammation; smoking; alcoholism; depression
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Muñoz, M.; Coveñas, R. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: a New Therapeutic Approach. Cancers 2015, 7, 1215-1232.

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