Zusammenfassung
Das aktuelle Therapiekonzept zur Behandlung des fortgeschrittenen Ovarialkarzinoms
der FIGO-Stadien III und IV besteht aus einer chirurgischen Tumorresektion mit sich
anschließender Chemotherapie. Die First-Line-Chemotherapie des Ovarialkarzinoms setzt
sich aus einer Kombination eines Taxans, z. B. Paclitaxel, mit einer Platinverbindung,
z. B. Carboplatin, zusammen. Die Mehrzahl der Patientinnen entwickelt allerdings,
aufgrund der Entwicklung von Chemotherapieresistenz, ein Rezidiv. Es ist daher von
fundamentaler Bedeutung, die zellulären Mechanismen, die Resistenzen gegenüber Taxanen
und Platinverbindungen verursachen, aufzuklären. In den vergangenen Dekaden konnten
über die Entwicklung und experimentelle Untersuchung von verschiedenen In-vitro-Modellsystemen
diverse Faktoren gefunden werden, die an Resistenzen beteiligt sind, wie z. B. Mitglieder
aus der Familie der Adenosin Triphosphate Bindungs Cassette (ABC)-Transporter, Faktoren,
die an der Regulation des Zellzyklus und apoptotischer Signalwege beteiligt sind und
viele andere. Eine mögliche klinische Relevanz dieser Faktoren zur Prädiktion wurde
in vielfältigen klinisch-pathologischen Studien untersucht. Bisher wird die klinische
Bedeutung in der wissenschaftlichen Literatur sehr kontrovers diskutiert. Es sind
daher dringend weitere „translationale“ Studien erforderlich, die Erkenntnisse aus
der Grundlagenforschung für die klinische Praxis nutzbar machen können.
Abstract
Surgery followed by chemotherapy is the standard therapeutic treatment for advanced,
FIGO stage III and IV ovarian carcinoma. First-line chemotherapy for ovarian cancer
consists of a combination of a taxane, e.g., paclitaxel, and a platinum-containing
drug, e.g., carboplatin. However, the majority of patients suffering from ovarian
cancer will relapse due to the development of drug resistance. Thus, it is of major
importance to identify the cellular mechanisms that mediate resistance against taxanes
and platinum drugs. In the past decades various factors involved in these types of
drug resistance have been identified by the experimental investigation of in vitro
model systems, e.g., different members of the adenosine triphosphate binding cassette
(ABC)-transporter family, factors involved in the regulation of cell cycle and apoptosis,
and many others. These factors have also been analysed with respect to their potential
clinical impact as predictive factors in clinical settings. So far, the clinical relevance
of these factors is still controversially discussed in the scientific literature.
Further “translational” studies are therefore necessary which may help to transfer
knowledge from basic science into clinical practice.
Schlüsselwörter
Ovarialkarzinom - Chemoresistenz - Taxane - Cisplatin
Key words
ovarian cancer - drug resistance - taxanes - cisplatin
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Prof. Dr. med. Dr. rer nat. H. Lage
Charité Campus Mitte
Institute of Pathology
Charitéplatz 1
10117 Berlin
Email: hermann.lage@charite.de
