Use of PARP Inhibitor in Cancer Cell Progression

Abstract

DNA damage response (DDR) is the cellular mechanism plays specific role of repairing during genotoxic injuries through specific mechanism of action. The DDR defects involve genomic instability and enhance tumor progression but when molecular alterations occurs in the cells become more susceptible to the pharmacological inhibition of the DNA repairing enzymes.Targeting cellular proteins like poly-ADP-ribose polymerase (PARPs) alters protein structure and function and favors molecular defects of the DDR process by bringing a specific lethality in DDR defective cancer cells and represents an anti-cancer strategy.Normal cells can bear the DNA damage produced by PARP inhibition due to an effective homologous recombination mechanism (HR); similarly, cancer cells with lacking HR become sensitive to the PARP inhibitors (PARPi) effects as they also lack the repairing mechanism of DSBs.

Keywords: DNA damage response, genotoxic, PARP, homologous recombination