Targeting the Sonic Hedgehog Signaling Pathway of Cancer Stem Cells to Treat Glioblastoma

Glioblastoma is an aggressive malignant brain tumor, and its five-year relative survival rate for patients is only 6.8 percent. In addition, almost all glioblastomas recur even after intensive treatments including surgery, radiation and chemotherapy, which are believed to be attributed to cancer stem cells (CSCs), a small population of cells existing in a tumor with ability to self-renewal and differentiation. Of multiple signaling pathways, sonic hedgehog signaling is one critical pathway involved in CSCs regulation. Therefore, targeting the sonic hedgehog signaling represents a novel therapy to treat glioblastomas, and significant efforts have been made in recent years to develop the sonic hedgehog signaling inhibitor drugs. This article specifically focuses on recent advances in the sonic hedgehog signaling inhibitor drug development by targeting multiple components of the signaling cascade including sonic hedgehog ligand, Smoothened (SMO) and GLI. Those inhibitors hold a great promise to destroy glioblastoma CSCs and prevent and treat tumor recurrence in the future.