Hedgehog pathway targets for potential therapeutic attack. (A) GLI1 activation is central in the Hh pathway. In the absence of mutations, canonical GLI1 activation occurs following binding of Hh protein to Ptch receptor and consequent activation of SMO. GLI1 can also be induced by PKA, PKC, or PI3K/AKT (SMO-independent GLI1 activation). Hh signaling can be inhibited by constructs that target SMO or by inhibitors of GLI1-induced transcription. (B) GANT61 is a GLI1 antagonist that inhibits GLI1-induced transcription by binding to the GLI1 consensus sequence in the promoters of the target genes.