The finding that a novel dual HDAC/SMO inhibitor, NL-103, can down-regulate both HH/GLI and HDAC activity, thereby overcoming vismodegib resistance [99], exemplifies that dual targeting of GLI and GLI promoting signals such as HDACs with a single compound is feasible and an attractive option for future therapeutic strategies including the treatment of AML patients. Here, GLI1 is linked to acute myeloid leukemia.