Liver Cancer Stem Cells: A New Paradigm for Hepatocellular Carcinoma Treatment

Abstract

Hepatocellular carcinoma (HCC) ranks as fifth most prevalent cancer worldwide. Despite its high prevalence rate the therapeutic options and prognosis of the patients mainly depend on the stage on the presentation. The Cancer Stem Cell (CSC) hypothesis proposes that a small population of cells is responsible for tumour development and disease progression. These cells are characterized by their ability of self-renewal, differentiation, chemo- and radio-resistance. CSC hypothesis could explain HCC heterogeneity within or between masses, its mechanism of recurrence and metastasis, and the poor outcome of current therapies. Due to their role in HCC it might be essential targeting these cells as part of the treatment. Several signaling pathways including RAS/RAF/MAPK, Wnt-β-catenin, PI3K/mTOR, among others; have been implicated in HCC carcinogenesis and their components represent novel molecular therapeutic targets. Because of the heterogeneity of these cancers and the complex process involved in hepatocarcinogenesis, our group and others suggest that combined therapy should be essential in HCC treatment. This review focuses on the current understanding of liver cancer stem cells, their clinical implications, and the rationale for targeting these cells in HCC treatment.