In summary, our results show that lurbinectedin efficiently takes advantage of the tumorigenic properties of SCLC cells by hindering the aberrantly high rate of transcriptional activity mediated by both ASCL1 and NEUROD1 and downregulated target genes commonly overexpressed in SCLC, finally impairing oncogenic programs and forcing SCLC cell apoptosis. Here, NEUROD1 is linked to small cell lung carcinoma.