Figure 1 - BRCA2 as a therapeutic target.

(a) Loss of BRCA2 results in ineffective DNA repair, which in turn results in the generation and accumulation of mutations that cause cancer. (b) BRCA2 deficiency can be exploited therapeutically by agents that lead to double-stranded DNA breaks, such as cisplatin. Substantial DNA damage results in the selective cell death of BRCA-deficient cells. (c) PARP can be targeted with small molecule inhibitors, leading to an accumulation of single-stranded DNA breaks, which can subsequently result in lethal double-stranded DNA breaks in the absence of BRCA2. Not shown: Restoration of BRCA2 renders cells insensitive to cisplatin and PARP inhibitors.