Fig. 3.

Illustration of abnormal pathways and potential targets in CSCs. FZD antagonists target either the Wnt proteins or FZD receptor complexes to inhibit the ligand-receptor interactions in both canonical and non-canonical Wnt pathway. DVL inhibitors block the DVL-PDZ interaction, resulting in subsequently inhibition of the signal transduction pathway. Tankyrase inhibitors stabilize Axin via inhibition of its proteasomal degradation, conversely resulting in increased degradation of β-catenin. CK1 agonists selectively potentiate CK1 kinase activity and stabilize the β-catenin destruction complex that decreasing Wnt signaling. β-catenin/TCF regulators inhibit Wnt-mediated transcriptional activity. LRP5/6 inhibitors competitively bind to the LRP5/6-sclerostin complex thus reverse the activation of Wnt/β-catenin signaling. ROR1-inhibitors ameliorate the access activated Wnt-signaling-mediated cancer cell proliferation, invasion, and therapy resistance. Potential anticancer therapeutic agents targeting the Notch pathway include targeting Notch ligands or receptors, inhibitors of the γ-secretase complex, and inhibitors of NICD-interacting transcriptional complex. SMO inhibitors block the Hh signaling by cyclopamine-competitively binding to SMO. GLI inhibitors prevent the transportation of GLI protein to nucleus thus decreased tumorigenesis gene expression. Inhibition of STAT3 and PI3K blocks their interactions with self-renewal pathways to facilitate CSCs eradication