Targeting Wnt-β-Catenin Signaling Pathway for Hepatocellular Carcinoma Nanomedicine

Abstract

Hepatocellular carcinoma (HCC) represents a high-fatality cancer with a 5-year survival of 22%. The Wnt/β-catenin signaling pathway presents as one of the most upregulated pathways in HCC. However, it has so far not been targetable in the clinical setting. Therefore, studying new targets of this signaling cascade from a therapeutic aspect could enable reversal, delay, or prevention of hepatocarcinogenesis. Although enormous advancement has been achieved in HCC research and its therapeutic management, since HCC often occurs in the context of other liver diseases such as cirrhosis leading to liver dysfunction and/or impaired drug metabolism, the current therapies face the challenge of safely and effectively delivering drugs to the HCC tumor site. In this review, we discuss how a targeted nano drug delivery system could help minimize the off-target toxicities of conventional HCC therapies as well as enhance treatment efficacy. We also put forward the current challenges in HCC nanomedicine along with some potential therapeutic targets from the Wnt/β-catenin signaling pathway that could be used for HCC therapy. Overall, this review will provide an insight to the current advances, limitations and how HCC nanomedicine could change the landscape of some of the undruggable targets in the Wnt/β-catenin pathway.

Keywords: HCC Targeting; Hepatocellular Carcinoma; Liver Cancer; Nanoparticle; Wnt Signaling.

Graphical abstract

Figure 1

Fate of nanoparticles in the HCC tumor cell.

Figure 2

Targeting strategies to HCC tumor cells.

Figure 3

Wnt/β-catenin signaling in HCC. (A) Wnt signaling pathway in the presence and absence of Wnt ligands; (B) Wnt ligands, targets and inhibitors.