γ-secretase inhibitors in solid tumor malignancies

The Notch pathway, like other developmental pathways such as hedgehog and Wnt, has diverse pleiotropic functions. The Notch pathway has a well-recognized role in hematological malignancies and recent research has also established a similar role in multiple solid tumors. This pathway has since received widespread attention as a promising target for cancer therapy. Here we provide a comprehensive overview of the pathway and review the role of the Notch pathway in the initiation, maintenance and progression of cancer. We further discuss the role of inhibitors of γ-secretase, a key enzyme of this pathway, in cancer therapy, with an emphasis on ongoing and recently completed trials assessing these agents in multiple tumor types.