PARP Inhibitors for Recurrent Ovarian Carcinoma: Current Treatment Options and Future Perspectives

Abstract

More than simply a promising management option, PARP inhibitors can be regarded as a milestone in the development of personalised treatment of recurrent ovarian carcinoma. Their mechanism of action, known as “synthetic lethality”, is dependent on functional differences of the DNA repair mechanisms of healthy cells and tumour cells; cells that repair DNA damage less efficiently are particularly sensitive to PARP inhibitors. Olaparib, licensed for use this year, is the best-studied PARP inhibitor used for treatment of high-grade serous ovarian carcinoma (HGSC). The efficacy of PARP inhibitors appears to be increased when used in combination with other treatments.

Zusammenfassung

PARP-Inhibitoren stellen nicht nur eine sehr vielversprechende Behandlungsmöglichkeit dar, ihre Entwicklung kann zudem als Meilenstein bei der Einführung einer personalisierten Medizin in der Behandlung des rezidivierten Ovarialkarzinoms betrachtet werden. Ihre Wirkungsweise, auch als synthetische Letalität bezeichnet, beruht auf den unterschiedlichen Funktionalitäten der DNA-Reparaturmechanismen bei gesunden und Tumorzellen. Zellen, die eine verminderte Fähigkeit aufweisen, DNA-Schäden effizient zu reparieren, sind besonders sensitiv gegenüber PARP-Inhibitoren. Bei Olaparib handelt es sich um den beim High-grade, serösen Ovarialkarzinom (HGSC) inzwischen am besten untersuchten und seit diesem Jahr zugelassenen PARP-Inhibitor. Die Kombination von PARP-Inhibitoren mit anderen Therapieansätzen scheint die Effektivität der PARP-Inhibitoren zu steigern.

Key words

ovarian cancer - BRCA - molecular pathway - PARP inhibitors

Schlüsselwörter

Ovarialkarzinom - BRCA - Signaltransduktionsweg - PARP-Inhibitor

• References

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