First, exposure to OTX015 led to the up-regulation of genes that might reduce the anti-tumor activity of the BET inhibitor such as STAT3 and FGFR3 in both NSCLC and SCLC, NOTCH1 and its target HES6 in NSCLC, PIM2 in SCLCL: further studies are needed to understand the relationship between these genes and OTX015 and whether novel combinations with agents targeting these proteins can improve the response to the epigenetic compound. This evidence concerns the gene HES6 and non-small cell lung carcinoma.