Targeting HR repair with poly (ADP-ribose) polymerase inhibition results in tumor-specific synthetic lethality. Model depicting potential targeting of HR repair to increase the therapeutic index of anti-glioma treatment. Sequestration of BRCA1 to the cytoplasm inhibits repair of DSBs and sensitizes cells to DNA-damaging agents. Following DNA damage, BRCA1 facilitates the repair of DNA in the nucleus. By targeting BRCA1 subcellular location, tumor cells retain unrepaired damaged DNA and are subsequently sensitized to poly (ADP-ribose) polymerase inhibitors.