Targeting the Endocannabinoid System: From the Need for New Therapies to the Development of a Promising Strategy. What About Pancreatic Cancer?

Abstract

Pancreatic cancer is one of the most fatal malignancies, and therefore, new strategies, which aim at the improvement of the prognosis of this lethal disease, are needed. Many clinical trials have failed to improve overall survival. Nowadays, research is focused on advances provided by novel potential targets to efficiently enhance life expectancy. Cannabinoids, the active components of Cannabis sativa L., and their derivatives, have been reported as palliative adjuvants to conventional chemotherapeutic regimens. Cannabinoid effects are known to be mediated through the activation of cannabinoid receptors. To date, two cannabinoid receptors, cannabinoid receptor 1 and 2, have been cloned and identified from mammalian tissues. Cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells, due to their ability to selectively induce apoptosis of these cells. This review strengthens the perception that cannabinoid receptors might be useful in clinical testing to prognose and treat pancreatic cancer. Many studies have tried to describe the mechanism of cell death induced by cannabinoids. The aim of this review is to discuss the effects of cannabinoid receptors in pancreatic cancer in order to provide a brief insight into cannabinoids and their receptors as pancreatic cancer biomarkers and in therapeutic strategies.

Keywords: Endocannabinoid; cancer; cannabinoid; pancreatic; receptor; review; treatment.

Figure 1. PRISMA flow chart for the current study.

Figure 2. Mechanism of actions and anticancer effects of cannabinoid receptors. AC: Adenylyl cyclase; AKT: protein kinase B also known as AKT; ATF-4: Activating transcription factor 4; cAMP: cyclic adenosine monophosphate; CHOP: C-homologous protein; ERK: extracellular-signalregulated kinase; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; MEK: mitogen-activated protein kinase kinase; NF-ĸB: nuclear factor kappa-light-chain-enhancer of activated B-cells; NOS: nitric oxyde synthase; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; ROS: reactive oxygen species; TRIB3: Tribbles homolog 3.