Additionally, we find that this nickase-based, genotype-specific toxicity is not limited to MYCN-amplified neuroblastoma; we also demonstrate its efficacy in additional malignancies that exhibit gene amplifications such as ERBB2 (HER2)-amplified breast cancer, MYC-amplified non-small cell lung cancer, and MYC-amplified colorectal cancer. Here, MYCN is linked to neuroblastoma.