Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy
Giorgio Valabrega, Giulia Scotto, Valentina Tuninetti, Arianna Pani, Francesco Scaglione
Abstract
Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.
Topics & Concepts
Poly ADP ribose polymerasePharmacodynamicsPharmacologyDNA damagePolymeraseDNA repairNAD+ kinasePARP inhibitorDNAOvarian cancerChemistryMechanism of actionBiologyComputational biologyCancer researchBiochemistryCancerPharmacokineticsEnzymeGeneticsIn vitroPARP inhibition in cancer therapyDNA Repair MechanismsElectrostatic Discharge in Electronics