New Targets in Hepatocellular Carcinoma – Liver Cancer Stem Cells

Abstract

Hepatocarcinogenesis is a multistep process evolving from chronic hepatitis and cirrhosis to hepatocellular carcinoma. Recent advances in molecular methods have led to a growing understanding of the underlying mechanisms of hepatocarcinogenesis. Many lines of evidence have demonstrated that cancer stem cells (CSCs, or more appropriately, cancer propagating cells) residing within the bulk tumour are capable of self-renewal and maintaining tumour propagation. They are also capable of metastasis and chemo-resistance. CSCs are considered a pivotal target for the eradication of cancers. Hence besides killing the bulk tumour, there is a need to also target this specific CSC subpopulation for novel. Using in vitro and in vivo models, we have identified CD24 and CD47, among others, as novel liver cancer stem cell markers. They are functional liver CSC markers that drive hepatocarcinogenesis through specific signaling pathways. Genomic analysis of these liver CSCs will also be discussed. Some of our recent translational work targeting these markers has shown promising data in animal models and will be presented and discussed. This presentation attempts to highlight the importance of liver CSCs implicated in the pathogenesis of hepatocellular carcinoma as well as potential targets for therapy. Detailed understanding of the molecular pathogenesis is crucial for the development of new therapeutic approaches against hepatocellular carcinoma.