The hepatocellular carcinoma (HCC) is the second major reasons for death from cancer throughout the world. A subgroup of HCC occurs following WNT/β-catenin signaling disregulation. The incorrect activation of the WNT/β-catenin pathway is seen in about 1/3 of the HCC. In HCC, the β-catenin nuclear and cellular accumulation is an indication of focally activating the signaling of WNT/FZ in 33-67% of tumors.

The corresponding published articles in English were search on a database of PubMed by keywords of HCC, WNT/β-catenin pathway, anti-Wnt/β-catenin, sorafenib-resistant, combination therapeutic, treatment.

Upregulated Wnt/β-catenin pathway in HCC affects tumor initiating cells, drug resistance, tumor progression, and metastasis. There are ongoing studied for finding selective anticancer drugs to target components of the β-catenin pathway, but limited research is in the phase I clinical trials. Previous studies have shown that sorafenib can reduce the activity of the Wnt/β-catenin pathway in HCC cells. Sorafenib reduces the Wnt/β-catenin signal in liver cancer cells by modulating transcriptional activity and reducing the level of β-catenin protein. Prospero-related homeobox 1 (PROX1) can increase β-catenin expression and nuclear energy transfer, activate the Wnt/β-catenin pathway and make HCC cells more resistant to Sorafenib treatment.

Recent studies indicate the anti-tumor effects of anti-Wnt/β-catenin inhibitors in combination with sorafenib in HCC cells. The Wnt/β-catenin pathway suggest molecular target for treatment of HCC.