Mechanismen der Chemotherapieresistenz beim Ovarialkarzinom

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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