Consistently, the dual HDAC/SMO inhibitor NL-103 has been reported to successfully overcome vismodegib resistance in SMO-M2 and SMO-D473H mutants by downregulated GLI2 expression [188], and coadministration of the HDAC inhibitor SAHA and vismodegib improved therapeutic outcomes for multiple aerodigestive cancer cell lines [189] (Figure 5, mechanism 8). This evidence concerns the gene SMO and cancer.