PMID- 29606854
OWN - NLM
STAT- MEDLINE
DCOM- 20181001
LR  - 20190221
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 12
DP  - 2018
TI  - Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer.
PG  - 605-617
LID - 10.2147/DDDT.S130809 [doi]
AB  - Rucaparib is a potent small-molecule inhibitor of poly (ADP-ribose) polymerase 
      (PARP) proteins (PARP-1, PARP-2 and PARP-3) that play an important role in 
      repairing DNA damage and maintaining genomic stability. Tumors with mutations in 
      BRCA1/2 or other homologous recombination deficiency (HRD) genes are particularly 
      sensitive to PARP inhibitors because of "synthetic lethality", whereby a 
      therapeutic agent can take advantage of an intrinsic weakness in DNA repair. 
      Rucaparib has been investigated in several preclinical and clinical studies 
      showing promising activity in BRCA-mutant and BRCA-wild-type epithelial ovarian 
      cancers (EOCs). Dose-escalation Phase I studies have established the recommended 
      Phase II dose to be 600 mg twice a day for oral rucaparib. Phase II and III 
      studies have defined its role as treatment for BRCA-mutant recurrent high-grade 
      EOC and as maintenance treatment for platinum-sensitive relapsed EOC following 
      response to platinum-based chemotherapy. Genomic loss of heterozygosity has also 
      been investigated as a potential signature of HRD and as a potential predictive 
      biomarker of response. Treatment-induced adverse events (AEs) have been observed 
      in almost all patients treated with rucaparib, but mainly lower grade; with the 
      most common being nausea, vomiting, asthenia/fatigue, anemia and transient 
      transaminitis. The majority of AEs occurred early in treatment, were transient 
      and have been easily managed with supportive treatment, dose interruption or 
      discontinuation. This review will analyze the results of clinical trials 
      investigating efficacy and safety of rucaparib in patients with ovarian cancer.
FAU - Colombo, Ilaria
AU  - Colombo I
AD  - Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 
      University Health Network, Toronto, ON, Canada.
FAU - Lheureux, Stephanie
AU  - Lheureux S
AD  - Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 
      University Health Network, Toronto, ON, Canada.
FAU - Oza, Amit Manulal
AU  - Oza AM
AD  - Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 
      University Health Network, Toronto, ON, Canada.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180321
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (BRCA1 Protein)
RN  - 0 (BRCA1 protein, human)
RN  - 0 (BRCA2 Protein)
RN  - 0 (BRCA2 protein, human)
RN  - 0 (Indoles)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 8237F3U7EH (rucaparib)
SB  - IM
MH  - Animals
MH  - BRCA1 Protein/*genetics/metabolism
MH  - BRCA2 Protein/*genetics/metabolism
MH  - Carcinoma, Ovarian Epithelial
MH  - Female
MH  - Humans
MH  - Indoles/*therapeutic use
MH  - Neoplasms, Glandular and Epithelial/*drug therapy/genetics/metabolism
MH  - Ovarian Neoplasms/*drug therapy/genetics/metabolism
MH  - Poly(ADP-ribose) Polymerase Inhibitors/*therapeutic use
PMC - PMC5868608
OTO - NOTNLM
OT  - BRCA mutations
OT  - PARP inhibitor
OT  - homologous recombination deficiency
OT  - maintenance treatment
OT  - ovarian cancer
OT  - rucaparib
COIS- Disclosure The authors report no conflicts of interest in this work.
EDAT- 2018/04/03 06:00
MHDA- 2018/10/03 06:00
PMCR- 2018/03/21
CRDT- 2018/04/03 06:00
PHST- 2018/04/03 06:00 [entrez]
PHST- 2018/04/03 06:00 [pubmed]
PHST- 2018/10/03 06:00 [medline]
PHST- 2018/03/21 00:00 [pmc-release]
AID - dddt-12-605 [pii]
AID - 10.2147/DDDT.S130809 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2018 Mar 21;12:605-617. doi: 10.2147/DDDT.S130809. 
      eCollection 2018.