title: MAP kinases and the inflammatory signaling cascade as targets for the treatment of endometriosis?
abstract: BACKGROUND
  The pathogenesis of endometriosis, a common benign disease, remains ill-defined, although it is clear that chronic inflammation plays a crucial role through mitogen-activated protein kinase (MAPK) signaling pathways. All current medical therapies for endometriosis are antigonadotropic, and therefore have a contraceptive effect. A concerted research effort is hence warranted with the aim of delivering novel therapeutics that reduces disease symptoms without blocking ovulation.
  
  
  METHODS
  The authors review the complex pathogenic mechanisms of chronic inflammation in endometriosis and their relationships with MAPK pathways. The authors conducted a literature search of descriptive and functional targeted validation of MAPK in the pathogenesis of endometriosis. The effects of MAPK inhibitors, which constitute potential agents for future treatments, are also described.
  
  
  CONCLUSIONS
  Preliminary studies have highlighted a crucial role for MAPK in driving endometriosis-related inflammation. MAPK inhibitors exhibit potent activity in terms of controlling growth of endometriosis lesions both in vitro and in animal models. As MAPK inhibitors are known to have a multitude of undesirable side effects, their use in humans has to be approached with great care. Indeed, use of these drugs would probably be limited to short exposures prior to surgery in cases involving the most severe disease phenotypes.
authors.affiliation: a 1 Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique - Hôpitaux de Paris (AP- HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and Reproductive Medicine , 75679 Paris, France +33 1 58 41 36 72 ; pietro.santulli@cch.aphp.fr.|b 2 Université Paris Descartes, Sorbonne Paris Cité, Department "Development, Reproduction and Cancer," Institut Cochin , INSERM U1016, Equipe Pr Batteux, Paris, France.
authors.forename: Pietro
authors.initials: P
authors.lastname: Santulli
authors.affiliation: a 1 Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique - Hôpitaux de Paris (AP- HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and Reproductive Medicine , 75679 Paris, France +33 1 58 41 36 72 ; pietro.santulli@cch.aphp.fr.|b 2 Université Paris Descartes, Sorbonne Paris Cité, Department "Development, Reproduction and Cancer," Institut Cochin , INSERM U1016, Equipe Pr Batteux, Paris, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Marcellin
authors.affiliation: c 3 University of Siena, Obstetrics and Gynecology, Department of Molecular and Developmental Medicine , Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tosti
authors.affiliation: b 2 Université Paris Descartes, Sorbonne Paris Cité, Department "Development, Reproduction and Cancer," Institut Cochin , INSERM U1016, Equipe Pr Batteux, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chouzenoux
authors.affiliation: b 2 Université Paris Descartes, Sorbonne Paris Cité, Department "Development, Reproduction and Cancer," Institut Cochin , INSERM U1016, Equipe Pr Batteux, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cerles
authors.affiliation: a 1 Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique - Hôpitaux de Paris (AP- HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and Reproductive Medicine , 75679 Paris, France +33 1 58 41 36 72 ; pietro.santulli@cch.aphp.fr.|b 2 Université Paris Descartes, Sorbonne Paris Cité, Department "Development, Reproduction and Cancer," Institut Cochin , INSERM U1016, Equipe Pr Batteux, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Borghese
authors.affiliation: b 2 Université Paris Descartes, Sorbonne Paris Cité, Department "Development, Reproduction and Cancer," Institut Cochin , INSERM U1016, Equipe Pr Batteux, Paris, France.|d 4 Hôpital Cochin, Department of Immunology , AP-HP, 75679 Paris cedex 14, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
authors.affiliation: a 1 Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique - Hôpitaux de Paris (AP- HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and Reproductive Medicine , 75679 Paris, France +33 1 58 41 36 72 ; pietro.santulli@cch.aphp.fr.|b 2 Université Paris Descartes, Sorbonne Paris Cité, Department "Development, Reproduction and Cancer," Institut Cochin , INSERM U1016, Equipe Pr Batteux, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Chapron
mesh_terms: D000818:Animals; D015195:Drug Design; D004715:Endometriosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases
keywords: endometriosis; infertility; inflammation; mitogen activated protein kinases; non-hormonal treatments; pain