RESUMO
INTRODUCTION: PARP inhibitors have dramatically improved outcomes for ovarian cancer patients, transforming oncologists' armamentarium and fueling hope for more cures and longer survival. AREAS COVERED: The recent PARP inhibitor randomized trials of FDA approved PARP inhibitors for ovarian cancer, olaparib, rucaparib and niraparib, and implications for clinical care are discussed with a focus on toxicity and risks. PARP adds NAD polymers to DNA-binding proteins, improving survival of cells after DNA damage, and acting as a scaffold for important DNA Damage Response (DDR) enzymes. If this system is inhibited, PARP activation cannot support DNA repair when there is synthetic lethality from BRCA mutations or homologous repair dysfunction (HRD), and the accumulation of DNA damage can kill cancer and lead to the catastrophic complications of MDS/AML. Although the risk of AML can be a < 1% risk, the incidence of MDS/AML presently approaches 10% in patients with BRCA mutations, multiple prior lines of platinum therapy, and protracted exposure to PARP inhibitors. EXPERT OPINION: PARP inhibitors are a well-tolerated and exciting new class of agents that improve survival despite the risk of AML. Understanding of the biology has led to optimal use and potential new strategies for overcoming PARP resistance.
