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.
