For example, adenovirus- or AAV-mediated transfer of CRISPR effectors targeting various tumor suppressor genes was successfully applied to engineer SCLC in mice, showing that co-mutations in the RB-family members Rbl1 and Rbl2 [15], the lysine demethylase Kdm5a/Rbp2 [16] or Notch receptors Notch1 and Notch2 [17] enhance SCLC development initiated by combined Trp53 and Rb1 mutations. This evidence concerns the gene RB1 and small cell lung carcinoma.