Inducing Synthetic Lethality using PARP Inhibitors

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.

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