Incorporating PARP-inhibitors into clinical routine: A tailored treatment strategy to tackle ovarian cancer.
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 (Lynparza™, 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.
a Faculty of Medicine , Ghent University , Ghent , Belgium.
E
E
De Jaeghere
b Department of Radiation Oncology and Experimental Cancer Research , Ghent University Hospital , Ghent , Belgium.
K
K
Vandecasteele
c Center for Medical Genetics , Ghent University Hospital , Ghent , Belgium.
K
K
Claes
d Department of Gynaecology , Ghent University Hospital , Ghent , Belgium.|e Department of Gynaecology , The Middelheim Hospital , Antwerp , Belgium.
A
A
Makar
d Department of Gynaecology , Ghent University Hospital , Ghent , Belgium.
P
P
Tummers
f Department of Medical Oncology , Ghent University Hospital , Ghent , Belgium.
V
V
Cocquyt
f Department of Medical Oncology , Ghent University Hospital , Ghent , Belgium.
Hannelore
H
Denys
D003536:Cystadenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010793:Phthalazines / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*
D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531550:olaparib
BRCA; Olaparib; Ovarian cancer; PARP-inhibitors; Targeted therapy