PARP inhibitors in the treatment of ovarian cancer

02/2017

MUDr. Libor Ševčík, Ph.D.

Onkogynekologická ambulance ONKOGYN s.r.o., Ostrava

SUMMARY

Ovarian cancer is among gynecological tumors the most common cause of death and the fifth in deaths among oncological diseases. In the last decade there have been significant advances in genomic mapping of tumor cells and in the knowledge of molecular mechanisms in the pathogenesis of ovarian cancer. Targeted molecular therapy starts to apply in addition to cytotoxic chemotherapy. Widely researched and promising possibility of targeted treatment of ovarian cancer are PARP inhibitors olaparib, veliparib, niraparib, rucaparib and talazoparib that are examined in monotherapy and in combination with other molecules as potential amplifiers or cytotoxic damage during chemotherapy or radiation treatment. Poly(ADP-ribose)-polymerase (PARP) inhibitors cause targeted tumour cell death in homologous recombination (HR)-deficient cancers, including gene BRCA1, BRCA2 mutated tumours, by exploiting synthetic lethality. Among the five key PARP inhibitors currently in clinical development, olaparib has undergone the most extensive clinical investigation. PARP inhibitors have demonstrated durable antitumour activity in BRCA1/2 mutated advanced ovarian cancer as a single agent in the treatment and maintenance setting, particularly in platinum sensitive disease. Current research is extending the use of PARP inhibitors beyond BRCA1/2 mutations to other sensitising molecular defects that result in HR-deficient cancer.

KEY WORDS

ovarian cancer, BRCA mutation, PARP inhibitor, synthetic lethality