A mechanism whereby aberrant Shh signaling converges on the Akt1-mTOR pathway, conferring selective growth advantage and enhanced survival of tumor cells has been identified. Utilizing a mouse model of BCNS, a pivotal role has been discovered for Akt1 signaling in BCC tumorigenesis. Based on the results described here certain embodiments are directed to methods and pharmaceutical formulations for treating BCC/BCNS, other cancers that are Shh+ and Akt+, cancers that are Shh+ and mTOR plus and cancers that are Shh+ by administering therapeutically effective amounts of various combinations of Akt inhibitors, Shh pathway inhibitors such as SMO inhibitors, and mTOR inhibitors.
