• BET inhibitors promote apoptosis and directly inhibit BCL2 and MYCN in an in vitro cell line. Oral administration of inhibitors inhibits tumor growth in a mouse xenograft model.• The combined inhibition of BET and MEK demonstrated synergistic effects in the majority of neuroblastoma cell lines under in vitro conditions, but exhibited limited antitumor activity in vivo. Here, BCL2 is linked to neoplasm.