Considering that both GDC-0449 and LDE-225 inhibit the Hh pathway activity by targeting Smo, it is not surprising that they are primarily insensitive for cancers harboring aberrant Hh activity caused by genetic alterations in key components downstream of ptch, such as activating mutations in Smo, loss of Sufu, or Gli2 gene amplification [5,6]. Here, SMO is linked to cancer.