Ciência e terapia do câncer

Molecular Mechanisms of PARP Inhibitors in BRCA-related Ovarian Cancer

Abstract

Toss A and Cortesi L

Ovarian cancer continues to be the main cause of death among all gynecological tumors. After standard treatments, most of patients are destined to recur within a short period, thus new therapies are urgently needed. The increasing knowledge of molecular mechanisms in ovarian cancer pathogenesis allowed identifying several targeted agents that are now entering in clinical practice. The family of poly(ADP-ribose) polymerase inhibitors represents a widely investigated and promising alternative for the targeted therapy of ovarian malignancies. PARP inhibitors exploit the synthetic lethality concept to prevent the repair of DNA damage, causing cancer cell death. This review describes the molecular mechanisms at the basis of PARP inhibition, particularly in BRCA-related ovarian malignancies and analyzes the main agents under investigations in preclinical and clinical studies.