Endometriosis, Ovarian Cancer and Mrp4, Is There A Truth Correlation?

Endometriosis is a hormonal and immune system disease in which cells similar to endometrium grow outside the uterine cavity. Etiopathogenesis is not well known yet, "retrograde menstruation” is the most accepted theory, after migrating, PGE2 promotes adhesion and invasion of the endometrium on other tissues. Prostaglandins are produced from arachidonic acid through the path of COX 1 and 2 that are inhibited by aspirin and other NSAIDs. A molecular difference between eutopic and ectopic endometrium is the over expression of the multidrug resistance–associated protein 4 (MRP4) in endometriosis. MRP4 plays a role in modulating some drugs, like aspirin and some drugs used for chemotherapy of ovarian cancer. At the same time, studies have been published on aspirin resistance and because of MRP4 is over expressed in human endometriotic cells (23), we think that it modulates the action of both some NSAIDs and aspirin even in the endometrium, so the COX1 and 2, are not modulated, as well as PGE2, which remains high in such cells.The aim of this review is to propose a possible correlation between MRP4 and resistance to drugs used in chemotherapy for ovarian cancer, including cancers developed from endometriotic implants. Our findings seem to support our idea of the possible correlation between MRP4 and resistance to drugs used in chemotherapy for ovarian cancer, including cancers developed from endometriosis implants. So, it would be appropriate to assess whether the use of NSAIDs for endometriosis, might cause a resistance to chemotherapy, for possible development of ovarian cancer from endometrioma, to make it possible, in the future, to treat better patients with endometriosis and avoid a possible development of resistance to chemotherapy drugs because of NSAIDs.