The YB-1 downstream pathways- diagnostic and therapeutic approaches for endometriosis -

Endometriosis is a complex gynecological disease widely recognized as an important women s health issue. Although conservative surgery as laparoscopy procedure and medical therapies are still known to be the best available treatment of endometriosis, they are non-curative and cannot prevent the recurrence of disease as well as related painful symptoms at long-term follow-up. An increased understanding of the molecular aspects in endometriosis would be beneficial in searching novel therapeutic strategies. Particularly, YB-1 has been considered of particular interest in many types of human tumors due to its pivotal role in transcriptional and translational regulation of multiple molecules involved in cellular homeostasis, as well as its significant association with therapy resistance and recurrence. A previous study of our group has revealed the involvement of YB-1 in endometriosis pathogenesis and its critical role in endometriotic cell expansion and survival in vitro. From this knowledge, we believe that YB-1 deserves a special attention in endometriosis and we aim to explore the YB-1 downstream pathways with respect to mechanisms of endometriotic cell survival, progression and invasion. In addition, we are prompting to test the phosphoinositide-dependent kinase-1 inhibitor 2-amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-acetamide (OSU-03012) for endometriosis treatment in a mouse model based on its ability to indirectly block the function of YB-1 and, consequently, YB-1-responsive genes in cancer cells. This study could provide a novel and promising therapeutic approach for endometriosis patients.

OSU-03012 konnte die Proliferation von Endometriosezellen in vitro und von Endometrioseimplantaten in vivo im Mausmodell durch eine Unterbrechung der Y-box-binding Protein 1 Funktion hemmen. Dies war verbunden mit reduzierten p-YB-1-Leveln. In unseren Studien konnten bereits sehr niedrige Dosierungen diesen Effekt erreichen, signifikante Nebenwirkungen traten nach 2 Wochen der Behandlung nicht auf.