Targeting cancer stem cells by inhibiting signaling pathways for cancer treatment

The Wnt, Hedgehog (HH), and Notch pathways are three critical evolutionarily conserved signaling pathways in typical embryogenesis and hemostasis. However, dysregulation of these pathways is apparent in multiple tumor types. Specifically, abnormal activation of these pathways is implicated in the regulation of cancer stem cells (CSCs). CSCs are characterized by the capacity of tumor initiation,self-renewal, form differentiated heterogeneous tumor cells, and develop resistance to therapy. As CSCs can survive traditional cancer therapies, eradication of CSCs in tumors may represent an effectiveanticancer therapeutic strategy. To aim this goal, new experimental agents are being produced to block Wnt, Notch, and HH signaling by CSCs, some of which are either approved by FDA or under clinicaltrials. As Wnt signaling activation is accountable for CSC’s self-renewal, focusing on CSCs by inhibiting this pathway may be a promising therapeutic approach for cancer. Two new classes of molecules that inhibit wnt pathway have been identified. The first is an acyltransferase that represses the activity of Porcupine, a fundamental molecule for wnt synthesis. The second inhibits the destruction of axin, asuppressor of wnt signaling activity. Moreover, there are other agents that target Frizzled (FZD) receptor or binds Wnt ligands and keeps them from binding to FZD receptors. Inhibiting HH pathwayinduces CSC’s differentiation and might be a fascinating approach for preventing tumor relapse. A couple of HH signaling inhibitors that are actively being tested in clinical trials include SMO and GLIInhibitor.

Keywords:

Cancer Stem Cells , Stem Cells and Cancer , Cancer Treatment and Management , Targeted Cancer Therapy , Drugs and Cancer