Chapter title |
Olaparib
|
---|---|
Chapter number | 15 |
Book title |
Small Molecules in Oncology
|
Published in |
Recent results in cancer research Fortschritte der Krebsforschung Progrès dans les recherches sur le cancer, January 2018
|
DOI | 10.1007/978-3-319-91442-8_15 |
Pubmed ID | |
Book ISBNs |
978-3-31-991441-1, 978-3-31-991442-8
|
Authors |
Sylvia Bochum, Stephanie Berger, Uwe M. Martens, Bochum, Sylvia, Berger, Stephanie, Martens, Uwe M. |
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. |
X Demographics
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Unknown | 1 | 100% |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
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Ireland | 1 | <1% |
Romania | 1 | <1% |
Unknown | 162 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 25 | 15% |
Student > Ph. D. Student | 14 | 9% |
Researcher | 11 | 7% |
Student > Master | 10 | 6% |
Other | 8 | 5% |
Other | 17 | 10% |
Unknown | 79 | 48% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 23 | 14% |
Biochemistry, Genetics and Molecular Biology | 23 | 14% |
Pharmacology, Toxicology and Pharmaceutical Science | 14 | 9% |
Chemistry | 6 | 4% |
Agricultural and Biological Sciences | 5 | 3% |
Other | 7 | 4% |
Unknown | 86 | 52% |