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

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 (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.

Keywords:

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