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International Journal of Clinical Oncology

Erschienen in:

22.06.2017 | Invited Review Article

Targeting DNA repair and replication stress in the treatment of ovarian cancer

verfasst von: Junko Murai

Erschienen in: International Journal of Clinical Oncology | Ausgabe 4/2017

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Abstract

Approximately half of high-grade serous epithelial ovarian cancers incur alterations in genes of homologous recombination (BRCA1, BRCA2, RAD51C, Fanconi anemia genes), and the rest incur alterations in other DNA repair pathways at high frequencies. Such cancer-specific gene alterations can confer selective sensitivity to DNA damaging agents such as cisplatin and carboplatin, topotecan, etoposide, doxorubicin, and gemcitabine. Originally presumed to inhibit DNA repair, PARP inhibitors that have recently been approved by the FDA for the treatment of advanced ovarian cancer also act as DNA damaging agents by inducing PARP–DNA complexes. These DNA damaging agents induce different types of DNA lesions that require various DNA repair genes for the repair, but commonly induce replication fork slowing or stalling, also referred to as replication stress. Replication stress activates DNA repair checkpoint proteins (ATR, CHK1), which prevent further DNA damage. Hence, targeting DNA repair genes or DNA repair checkpoint genes augments the anti-tumor activity of DNA damaging agents. This review describes the rational basis for using DNA repair and DNA repair checkpoint inhibitors as single agents. The review also presents the strategies combining these inhibitors with DNA damaging agents for ovarian cancer therapy based on specific gene alterations.

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Titel: Targeting DNA repair and replication stress in the treatment of ovarian cancer
verfasst von: Junko Murai
Publikationsdatum: 22.06.2017
Verlag: Springer Japan
Erschienen in: International Journal of Clinical Oncology / Ausgabe 4/2017
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-017-1145-7

Springer Medizin

Targeting DNA repair and replication stress in the treatment of ovarian cancer

Abstract

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