MAP kinases and the inflammatory signaling cascade as targets for the treatment of endometriosis?

Abstract

Introduction: 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.Areas covered: 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.Expert opinion: 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.