WNT/β-catenin pathway activation in hepatocellular carcinoma: a clinical perspective
Li Ma, Wei Wei, Mei-Sze Chua, Samuel So
Asian Liver Center and Department of Surgery, Stanford University School of Medicine, Stanford University, Stanford, CA, USA
Abstract: Hepatocellular carcinoma (HCC) is a significant global health concern which requires multidisciplinary approaches in its management. However, apart from surgical resection of the tumor, molecularly targeted therapeutics remains limited to sorafenib. New targets and drugs are urgently needed to broaden the currently limited treatment options for HCC to allow more efficacious clinical interventions and ultimately to improve the overall survival of HCC patients. The WNT/β-catenin pathway controls multiple biological functions throughout embryonic development and adult homeostasis; its dysregulation underlies a wide range of pathologies including cancer. In particular, many lines of evidence suggest that hyperactivation of this pathway is associated with the initiation and development of HCC. The critical role of the WNT to WNT/β-catenin pathway in HCC lends itself to rationally designed approaches to intervene with various aberrant loci along its signaling cascade to achieve therapeutic effects in HCC. Here, we review the current state of knowledge on WNT/β-catenin pathway deregulation in HCC, and how this pathway may be exploited for therapeutic interventions.
Keywords: WNT/β-catenin signaling, hepatocarcinogenesis, β-catenin/TCF complexes, targeted therapy
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