Abstract
The enzyme poly(ADP)-ribose polymerase-1 (PARP-1) plays an important role in the repair of DNA damage via a mechanism called base excision repair (BER). Initially, inhibition of PARP-1 showed to be a promising anti-tumor strategy in preclinical models using BRCA1 and BRCA2 deficient tumor cell lines. More recently, several small molecules targeting PARP-1 entered the clinic and demonstrated compelling anti-tumor activity in patients with BRCA deficient breast and ovarian cancers, and in patients with triple-negative breast cancer. In this review we aim to summarize the most recent advances in the development of PARP inhibitors, with a focus on the clinical data.
Keywords: Synthetic lethality, repair mechanism, PARP, BRCA deficient, olaparib
Current Clinical Pharmacology
Title: Inducing Synthetic Lethality using PARP Inhibitors
Volume: 5 Issue: 3
Author(s): David S. Boss, Jos H. Beijnen and Jan H.M. Schellens
Affiliation:
Keywords: Synthetic lethality, repair mechanism, PARP, BRCA deficient, olaparib
Abstract: The enzyme poly(ADP)-ribose polymerase-1 (PARP-1) plays an important role in the repair of DNA damage via a mechanism called base excision repair (BER). Initially, inhibition of PARP-1 showed to be a promising anti-tumor strategy in preclinical models using BRCA1 and BRCA2 deficient tumor cell lines. More recently, several small molecules targeting PARP-1 entered the clinic and demonstrated compelling anti-tumor activity in patients with BRCA deficient breast and ovarian cancers, and in patients with triple-negative breast cancer. In this review we aim to summarize the most recent advances in the development of PARP inhibitors, with a focus on the clinical data.
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Cite this article as:
S. Boss David, H. Beijnen Jos and H.M. Schellens Jan, Inducing Synthetic Lethality using PARP Inhibitors, Current Clinical Pharmacology 2010; 5 (3) . https://dx.doi.org/10.2174/157488410791498798
DOI https://dx.doi.org/10.2174/157488410791498798 |
Print ISSN 1574-8847 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3938 |
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