MAP2K1 and colorectal carcinoma: 39 This depletion of NAD+ leads to the induction of double-strand DNA breaks and promotes apoptosis by caspase-3 cleavage, thereby reducing the development of therapeutic resistance in ovarian cancer.39 Selumetinib (Koselugo) is an orally administered selective inhibitor of MEK 1 and 2,40 which are components of the MAPK signaling pathway.41 Song et al42 found that the combination of Selumetinib with hesperetin enhances the inhibitory effects on the MAPK signaling pathway in CRC.