Points of Therapeutic Intervention along the Wnt Signaling Pathway in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third most common cause related to cancer mortality worldwide. Due to frequently late diagnosis, overall prognosis of patients with liver cancer is poor. Unfortunately, there is no targeted therapeutics for the treatment of HCC except sorafenib, which has exhibited notable results in certain advanced HCC. Increasing evidences indicate that deregulation of Wnt/β-catenin signaling pathway plays a critical role in hepatic oncogenesis and mainly occurs at the early stage of hepatocarcinogenesis. In addition, aberrant activation of the Wnt/β- catenin signaling pathway has been linked with more aggressive HCCs. The major mechanism for aberrant activation of the signaling in HCC is caused by genetic mutations and/or altered expression of upstream components of the Wnt/β-catenin signaling. This leads to abnormal expression of the β-catenin/TCF-responsive target genes, which regulate cell growth, apoptosis, cell motility, and invasion. Thus, intervention of the Wnt/β-catenin signaling activity can be potential therapeutics for HCC. This review will discuss the identified potential molecular targets related to the Wnt/β-catenin signaling pathway and their potential therapeutic applications.

Keywords: β-catenin, Canonical Wnt, Dishevelled, Frizzled receptor, Glypican-3, Hepatocellular carcinoma, Immunotherapy, Molecular target, Porcupine, Small molecule inhibitor, Tankyrase, Targeted therapy, T-cell factor, Wnt ligand, Wnt signaling.