Go J Yoshida
The response to Hh signal inhibitors such as cyclopamine and vismodegib depends on the cell context. When tumor cells constitutively activate Hh signal with loss-of-functional mutation of PTCH gene or gain-of-functional mutation of Gli1 transcriptional factor, the cells are not likely to show any response. On the other hand, when they do not harbor mutation to cause "signal addiction", the administration of inhibitors resuuts in the reduction of the target molecules of Gli1, thus the negative feedback machinery might work. That is why cyclopamine and vismodegib induce the compensatory down-regulation of the negative regulator PTCH to maintain the range of Hg signal activity.
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