Specific killing of BRCA1-deficient cancer cells by depletion of EXO1
![Specific killing of BRCA1-deficient cancer cells by depletion of EXO1](/media/2257/haico-van-attikum_16-marzo.jpg)
Haico van Attikum
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
BRCA1 and BRCA2 are essential genome maintenance factors that function in the repair of DNA Double-Strand Breaks (DSBs) by homologous recombination (HR). Cancer patients that carry tumors with loss-of-function mutations in BRCA1 or BRCA2 often benefit from treatment with PARP inhibitor therapy, which specifically kills HR-deficient tumor cells. However, clinical responses are rarely long-lasting due to resistance to PARP inhibitor treatment. We therefore sought to identify novel therapeutic opportunities to treat HR-deficient tumors. Our studies revealed that genetic inactivation of the exonuclease EXO1 is severely toxic to BRCA1-deficient cells, but not to BRCA1-proficient cells. In my seminar I will present the mechanistic basis of this finding, highlighting EXO1 as a novel target with therapeutic potential for BRCA1-deficient tumors.