PARP inhibitors in ovarian cancer: Clinical evidence for informed treatment decisions

PARP Inhibitors in Ovarian Cancer

New treatment option for ovarian cancer: PARP inhibitors

Poly(ADP-ribose) polymerase (PARP), which was first described over 50 years ago by Mandel, are a family of protein enzymes involved in DNA damage response and works by recognizing the single-strand DNA break (ssDNA) and then effecting DNA repair. A double-strand DNA (dsDNA) break can be repaired by one of two different pathways: homologous recombination (HR) or non-homologous end joining (NHEJ)...

Molecular Mechanisms of PARP Inhibitors in BRCA-related Ovarian Cancer

Abbreviations: PARP: Poly(Adp-Ribose) Polymerase; SSBS: Single Strand Breaks; DSBS: Double Strand Breaks; BER: Base Excision Repair; NER: Nucleic Acid Excision Repair; MMR: Mismatch Repair; HR: Homologous Recombination; NHEJ: Non-Homologous End Joining; DNA-PKCS: DNA-Dependent Protein Kinase; ORR: Objective Response Rate; PFS: Progression-Free Survival; PLD: Pegylated Liposomal Doxorubicin; OS:...

PARP Inhibitors for Cancer Therapy

Rucaparib is an inhibitor of nuclear poly (ADP-ribose) polymerases (inhibition of PARP-1 > PARP-2 > PARP-3), following a similar drug, Olaparib. It disrupts DNA repair and replication pathways (and possibly transcription), leading to selective killing of cancer cells with BRCA1/2 mutations. Rucaparib is approved for recurrent ovarian cancers with germline or somatic mutations in BRCA1/2.

PARP Inhibitors in Epithelial Ovarian Cancer: State of Art and Perspectives of Clinical Research.

Homologous recombination (HR) and base excision repair (BER) are two of the major DNA-repair pathways. The proteins encoded by breast-related cancer antigen (BRCA) and poly(adenosine diphosphate-ribose) polymerases (PARP) are involved in HR and BER, respectively. Tumors with HR deficiency, including those in BRCA mutation carriers, are sensitive to BER blockade via PARP inhibitors. These repres...