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Olaparib

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Small Molecules in Oncology

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 211))

Abstract

Olaparib (Lynparza [AstraZeneca, Cambridge, UK], formerly referred to as AZD2281 or KU0059436) is an oral poly(ADP-ribose) polymerase (PARP) inhibitor. It is rationally designed to act as a competitive inhibitor of NAD+ at the catalytic site of PARP1 and PARP2, both members of the PARP family of enzymes that are central to the repair of DNA single-strand breaks (SSBs) mediated via the base excision repair (BER) pathway. Inhibition of the BER pathway by olaparib leads to the accumulation of unrepaired SSBs, which leads to the formation of deleterious double-strand breaks (DSBs). In cells with an intact homologous recombination (HR) pathway, these DSBs can be repaired effectively. However, in tumors with homologous recombination repair deficiencies, olaparib causes synthetic lethality through the combination of two molecular events that are otherwise nonlethal when occurring in isolation. Olaparib is already approved for the treatment of patients with recurrent ovarian cancer and a BRCA mutation, and it has been shown to provide clinically meaningful benefits among such patients. It has also shown promising activity in patients with metastatic breast or prostate cancer and a germline BRCA mutation. Besides its usage as a single agent, olaparib can also act either as a chemo- and/or radiosensitizer, due to its ability to potentiate the cytotoxic effects of these therapeutic agents. However, a clear patient benefit for the latter application has not been demonstrated yet.

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Authors and Affiliations

  1. Cancer Center Heilbronn-Franken, SLK-Kliniken Heilbronn GmbH and MOLIT Institute for Personalized Medicine, Am Gesundbrunnen 20–24, 74078, Heilbronn, Germany

    Sylvia Bochum, Stephanie Berger & Uwe M. Martens

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  1. Sylvia Bochum
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  2. Stephanie Berger
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  3. Uwe M. Martens
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Correspondence to Sylvia Bochum .

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  1. MOLIT Institute, Cancer Center Heilbronn-Franken, SLK-Clinics, Heilbronn, Baden-Württemberg, Germany

    Uwe M. Martens

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Bochum, S., Berger, S., Martens, U.M. (2018). Olaparib. In: Martens, U. (eds) Small Molecules in Oncology. Recent Results in Cancer Research, vol 211. Springer, Cham. https://doi.org/10.1007/978-3-319-91442-8_15

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  • DOI: https://doi.org/10.1007/978-3-319-91442-8_15

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