PARP inhibitors in the ovarian cancer therapy

PARP Inhibitors in Ovarian Cancer

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.

Resistance to PARP-Inhibitors in Cancer Therapy

The pharmacological inhibitors of poly(ADP-ribose) polymerase (PARP) family of proteins have shown promising results in preclinical studies and clinical trials as a monotherapy or in combination therapy for some cancers. Thus, usage of PARP-inhibitors (PARPi) in cancer therapy is bound to increase with time, but resistance of cancer cells to PARPi is also beginning to be observed. Here we revie...

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:...

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)...