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PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting

Przegla̜d menopauzalny, 2016-12, Vol.15 (4), p.215-219 [Peer Reviewed Journal]

Copyright Termedia Publishing House 2016 ;Copyright: © 2017 Termedia Sp. z o. o. 2017 ;ISSN: 1643-8876 ;EISSN: 2299-0038 ;DOI: 10.5114/pm.2016.65667 ;PMID: 28250726

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  • Title:
    PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting
  • Author: Dziadkowiec, Karolina N ; Gąsiorowska, Emilia ; Nowak-Markwitz, Ewa ; Jankowska, Anna
  • Subjects: BRCA ; DNA ; mutation ; olaparib ; ovarian cancer ; PARP ; PARP1 ; PARP2 ; poly(ADP-ribose) polymerases ; Review Paper
  • Is Part Of: Przegla̜d menopauzalny, 2016-12, Vol.15 (4), p.215-219
  • Description: Poly(ADP-ribose) polymerases have shown true promise in early clinical studies due to reported activity in BRCA-associated cancers. PARP inhibitors may represent a potentially important new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. In order to widen the prospective patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. In addition, a more sophisticated understanding of the toxicity profile is required if PARP inhibitors are to be employed in the curative, rather than the palliative, setting. PARP inhibitors have successfully moved into clinical practice in the past few years, with approval granted from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) within the past two years. The United States FDA approval of olaparib applies to fourth-line treatment in germline BRCA-mutant ovarian cancer, and European EMA approval of olaparib for maintenance therapy in both germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. This review covers the current understanding of PARP, its inhibition, and the basis of the excitement surrounding these new agents. It also evaluates future approaches and directions required to achieve full understanding of the intricate interplay of these agents at the cellular level.
  • Publisher: Poland: Termedia Publishing House
  • Language: English;Polish
  • Identifier: ISSN: 1643-8876
    EISSN: 2299-0038
    DOI: 10.5114/pm.2016.65667
    PMID: 28250726
  • Source: GFMER Free Medical Journals
    PubMed Central
    ProQuest Central
    DOAJ Directory of Open Access Journals
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