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

Miguel Muñoz,Rafael Coveñas

doi:10.3390/cancers7030832

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.

Highlights

IntroductionPancreatic cancer (PC), one of the most ominous types of cancer, is the fourth leading cause of cancer related-deaths in both men and women, with less than 5% survival at 5 years after diagnosis
Pancreatic cancer (PC), one of the most ominous types of cancer, is the fourth leading cause of cancer related-deaths in both men and women, with less than 5% survival at 5 years after diagnosis.In 2013, the American Cancer Society estimated that there were 45,220 new cases of PC in the UnitedStates and 38,460 deaths from the disease
The aimtheof above this paper is to review the involvement of the substance P (SP)/NK-1 system in these pathologies and, in particular, in PC

Summary

Introduction

Pancreatic cancer (PC), one of the most ominous types of cancer, is the fourth leading cause of cancer related-deaths in both men and women, with less than 5% survival at 5 years after diagnosis. Because there is still a lack of curative therapy there is An urgent need to prevent PC by applying new strategies and/or by improving current therapies [3] Research into this issue should focus on drugs with fewer side effects than those produced by cytostatic drugs and this can only be achieved if the drug is specific against PC cells. Smoking and alcohol abuse induce up-regulation present and in inflammation and in chronic pancreatitis. Of it has been reported thatand chronic stress increases issusceptibility a risk factor for for developing the development of PCand [7] accelerates (Figure 1).PC It has been reported pancreatitis growth and invasion [8,9]. Many data indicate that progression the SP/NK-1(Figure receptor system is involved in smoking, depression, chronic and cancer. The aimtheof above this paper is to review the involvement of the SP/NK-1 system in these pathologies and, in particular, in PC

Substance P and the NK-1 Receptor

Findings

Conclusions