The targeting of DDR proteins is broadly applicable even outside of a synthetically lethal context, such as with PARP dependence in BRCA1/2 mutation positive cancers, and numerous inhibitors against PARP1, ATR, Chk1, and MDM2 are being tested in combination with standard of care radiation and chemotherapy in the setting of medulloblastoma and beyond (160–162). The gene discussed is MDM2; the disease is cancer.