Update on the endocannabinoid system as an anticancer target

Expert Opin Ther Targets. 2011 Mar;15(3):297-308. doi: 10.1517/14728222.2011.553606. Epub 2011 Jan 19.

Abstract

Introduction: Recent studies have shown that the endocannabinoid system (ECS) could offer an attractive antitumor target. Numerous findings suggest the involvement of this system (constituted mainly by cannabinoid receptors, endogenous compounds and the enzymes for their synthesis and degradation) in cancer cell growth in vitro and in vivo.

Areas covered: This review covers literature from the past decade which highlights the potential of targeting the ECS for cancer treatment. In particular, the levels of endocannabinoids and the expression of their receptors in several types of cancer are discussed, along with the signaling pathways involved in the endocannabinoid antitumor effects. Furthermore, the beneficial and adverse effects of old and novel compounds in clinical use are discussed.

Expert opinion: One direction that should be pursued in antitumor therapy is to select compounds with reduced psychoactivity. This is known to be connected to the CB1 receptor; thus, targeting the CB2 receptor is a popular objective. CB1 receptors could be maintained as a target to design new compounds, and mixed CB1-CB2 ligands could be effective if they are able to not cross the BBB. Furthermore, targeting the ECS with agents that activate cannabinoid receptors or inhibitors of endogenous degrading systems such as fatty acid amide hydrolase inhibitors may have relevant therapeutic impact on tumor growth. Additional studies into the downstream consequences of endocannabinoid treatment are required and may illuminate other potential therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cannabinoid Receptor Modulators / metabolism*
  • Drug Delivery Systems*
  • Drug Design
  • Endocannabinoids*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / physiopathology
  • Receptor, Cannabinoid, CB1 / drug effects
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / drug effects
  • Receptor, Cannabinoid, CB2 / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2