title: The evolving role of the endocannabinoid system in gynaecological cancer.
abstract: BACKGROUND
  The 'endocannabinoid system' (ECS), comprising endogenous ligands (endocannabinoids) and their regulating enzymes, together with the cannabinoid receptors, has attracted a great deal of attention because it affects not only all facets of human reproduction, from gametogenesis through to parturition and beyond, but also targets key mechanisms affecting some hallmarks of cancer. Recent evidence showing that cannabinoid receptors play a very important role in the development of malignancies outside of the reproductive organs suggests a similar role for the ECS in the establishment or continued development of gynaecological malignancy.
  
  
  METHODS
  Primary papers and review articles, and primary sources within these papers, up to December 2014, on the evolving role of the ECS in cancer, with a special focus on gynaecological cancers, were obtained by Medline and PubMed searches using the search terms: 'cancer', 'cannabinoid', 'endocannabinoid', 'gynaecology' and 'malignancy'. Non-English manuscripts were excluded.
  
  
  RESULTS
  More than 2100 sources were obtained from which only 112 were specifically important to the topic. Analysis of those articles supports a role of the ECS in gynaecological cancers but leaves many gaps in our knowledge that need to be filled. How some of the relevant receptors are activated and cause changes in cell phenotypes that progress to malignancy remains undiscovered and an area for future research. Increasing evidence suggests that malignant transformation within the female genital tract could be accompanied by deregulation of components of the ECS, acting through rather complex cannabinoid receptor-dependent and receptor-independent mechanisms.
  
  
  CONCLUSIONS
  The paucity of studies in this area suggests that research using animal models is needed to evaluate endocannabinoid signalling in cancer networks. Future randomized clinical studies should reveal whether endocannabinoids or their derivatives prove to be useful therapeutic targets for gynaecological and other cancers.
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK.
authors.forename: Thangesweran
authors.initials: T
authors.lastname: Ayakannu
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK Biosciences, School of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham NG1 4BU, UK superdoc.at@gmail.com.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Taylor
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Willets
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK Department of Obstetrics and Gynaecology, Sidra Medical and Research Centre, Doha P.O. Box 26999, Qatar.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Konje
mesh_terms: D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000627:therapeutic use; D002186:Cannabinoids / Q000627:therapeutic use; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid
keywords: cancer; cervix; endocannabinoid; endometrium; ovary