NOTCH1 and neoplasm: Finally, functional studies employing perturbation sequencing, which combines Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-mediated gene perturbations with single-cell transcriptomic readouts, have revealed critical vulnerabilities and adaptive dependencies that tumor cells acquire upon loss of KEAP1, NFE2L2, or NOTCH1, thereby uncovering potential targets for therapeutic intervention [235,236].