SMO and pancreatic neoplasm: In 2010, it was found that medulloblastoma resistance towards SMO inhibitors decreased as a result of combination therapy with SMO and PI3K/AKT inhibitors [83], and recently, the combination of the SMO inhibitor, NVP-LDE-225 with the PI3K/mTOR inhibitor, NPV-BEZ-235 exhibited improved efficacy towards inhibition of self-renewal and tumorigenicity of human pancreatic cancer stem cells, compared to treatment with only one of the agents, [84].