DNA repair defects and therapeutic intervention in BRCA1/2 defective tumors. Following DNA damage poly(ADP-ribose) polymerases (PARP), specifically PARP-1 and PARP-2, are activated and bind to the exposed Single Strand Breaks (SSBs). Pharmacological inhibition of PARP1 with PARP-inhibitors leads to a block in the repair of SSBs, resulting in the blockage of replication fork and subsequent conversion of damage in DSBs. In hereditary cancers harboring BRCA1/BRCA2 mutations, this system is inefficient and therefore the tumor cells lacking this survival mechanism undergo cell death. The antitumor activity of PARP inhibitors may be enhanced by combination with chemotherapeutic agents which induce direct damage to DNA, such as platinum derivatives.