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  • 1 University of Pennsylvania Health System Department of Gynecologic Oncology Philadelphia
  • 2 Semmelweis Egyetem, Általános Orvostudományi Kar I. Szülészeti és Nőgyógyászati Klinika Budapest Baross u. 27. 1088
Open access

Az ováriumtumorok mortalitása a legmagasabb a nőgyógyászati tumorok között. Ez egyrészt a késői diagnózisnak, másrészt a hatásos terápia hiányának következménye. Az ováriumtumorok karcinogenezise és metasztázisképzése egy komplikált genetikai, molekuláris és biokémiai folyamatsor eredménye. A lizofoszfátsav (LPA) termelésének, receptorstátusának és szignáltranszdukciós útvonalának abnormalitása gyakran megtalálható az ováriumtumorokban, ami azt sejteti, hogy az LPA nagyon fontos szerepet játszik ennek a betegségnek a kialakulásában és patofiziológiájában. Így jogosan feltételezhetjük, hogy az LPA-szignálkaszkád számos célpontot szolgáltat a molekuláris kezelési módok kialakítására és jó példát mutat arra, hogyan lehet új diagnosztikus és terápiás módszereket kialakítani egyes betegségek ellen. Az LPA-t lebontó és termelő enzimcsaládoknak csak a közelmúltban történt felfedezése és a receptorspecifikus molekulák kifejlesztése új fejezetet nyithat e potenciálisan halálos betegség kezelésében. Ebben az összefoglaló tanulmányban ismertetjük, hogy a tumorsejtekben lévő LPA-t lebontó enzimek aktivitása csökkent, és ez hozzájárul a tumor progressziójához. Ugyanezen enzimek mesterségesen létrehozott, fokozott aktivitása csökkenti a tumorsejtek növekedését és elősegíti a fiziológiás viszonyok helyreállását. Bemutatjuk azokat az irodalmi adatokat, amelyek egyértelműen bizonyítják, hogy a lipidfoszfát-foszfatáz enzimek hatásukat a sejten kívüli LPA lebontásával érik el. Minthogy ez a lebontás extracellulárisan történik, ez megmagyarázza a „bystander-effect” előfordulását, amit szintén ismertetünk. Az LPA-lebontás és -termelés enzimjei, illetve az LPA-t kötő receptorok kitűnő célpontok új molekuláris terápia kidolgozására. A különböző LPA-izoformák és más lizofoszfolipidek szintváltozásainak korai detektálása segíthet a tumor korai diagnosztizálásában, illetve később a kezelés hatékonyságának követésében. A közelmúlt jelentős LPA-szignálkaszkáddal kapcsolatos kutatási eredményei azt sejtetik, hogy azok jelentős szerepet fognak játszani ennek a még mindig halálos betegségnek a kezelésében, de további kutatások szükségesek a részletek pontos megértéséhez.

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