The Endocannabinoid System as a Target in Cancer: Status and Future Perspectives

Abstract

The endocannabinoid system (ECS) represents a complex network of different molecules as cannabinoid receptors, endocannabinoid ligands, and the enzymatic machinery that drives their metabolism, as well as cells and pathways that use endocannabinoid signaling. It is important for the regulation of most vital biochemical processes contributing to and overall homeostasis state. As such, it is ambiguously implicated in both the development of cancer and its suppression, as well as its progression and interaction with current anti-cancer therapeutics. This work will review the main ECS components and their discovery, structure, pharmacological properties, and significance in various physiological and pathological states and focus on the current burden of evidence available from open-access databases, experimental data, and expert reviews which offer future directions for its use in the oncological setting. The vast potential of the translationally significant information of the so-called endocannabinoidome is currently being explored in many ongoing clinically oriented research studies as well as clinical trials. Previously acquired pharmacological data from its historical application in pain alleviation and as a general palliative agent in oncology will be useful for drug repurposing scenarios, aiming to speed up its possible clinical applications, after decades of carrying the stigma of an ethically and legally compromised target.