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Acta Clin Belg. 2017 Feb;72(1):6-11. doi: 10.1080/17843286.2016.1188455. Epub 2016 May 31.

Incorporating PARP-inhibitors into clinical routine: A tailored treatment strategy to tackle ovarian cancer.

Author information

1
a Faculty of Medicine , Ghent University , Ghent , Belgium.
2
b Department of Radiation Oncology and Experimental Cancer Research , Ghent University Hospital , Ghent , Belgium.
3
c Center for Medical Genetics , Ghent University Hospital , Ghent , Belgium.
4
d Department of Gynaecology , Ghent University Hospital , Ghent , Belgium.
5
e Department of Gynaecology , The Middelheim Hospital , Antwerp , Belgium.
6
f Department of Medical Oncology , Ghent University Hospital , Ghent , Belgium.

Abstract

DNA repair mechanisms play a key role in oncogenesis and cancer progression in women with BRCA mutation-positive (BRCAm) ovarian cancer (OC). The BRCA1/2 and poly(ADP-ribose) polymerase (PARP) proteins are considered the foremost mediators among the various components of double-strand and single-strand repair, respectively. A series of new therapeutic drugs that target PARP have been developed for BRCAm OC. This class of agents provokes tumour-specific cytotoxicity with minimal side effects by inducing synthetic lethality, of which they are the first clinical example. The European Medicines Agency granted accelerated licensing approval for the first-in-class-drug that inhibits PARP, olaparib (Lynparzaâ„¢, AstraZeneca). Olaparib can be used as a monotherapeutic maintenance treatment in patients with platinum-sensitive relapsed (germline and/or somatic) BRCAm high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer responsive to platinum-based chemotherapy. Seen in light of these recent events, this review article will focus on (a) how PARP-inhibitors exploit cancer-specific defects in the homologous recombination repair apparatus and (b) how BRCA testing is implemented in routine clinical care.

KEYWORDS:

BRCA; Olaparib; Ovarian cancer; PARP-inhibitors; Targeted therapy

PMID:
27267353
DOI:
10.1080/17843286.2016.1188455
[Indexed for MEDLINE]

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