Inducing synthetic lethality using PARP inhibitors.
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.
Boss
David S
DS
The Netherlands Cancer Institute, Department of Medical Oncology, The Netherlands.
Beijnen
Jos H
JH
Schellens
Jan H M
JH
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000172:deficiency / Q000235:genetics; D024682:BRCA2 Protein / Q000172:deficiency / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D000067856:Poly(ADP-ribose) Polymerase Inhibitors