Deciphering cancer stem cells in liver cancers: new tools with improved resolution.

Abstract

Hepatocellular carcinoma (HCC) is the major form of liver cancer in the world with the highest prevalence in Asia. Intra-tumoral heterogeneity is a fundamental characteristic of liver cancer that impacts on its disease progression and treatment response. The cancer stem cell (CSC) subpopulation is one of the driving forces of tumor cell heterogeneity because it can regenerate cells of different properties as to maintain the tumor bulk of origin. Tremendous effort has been made in the past two decades to identify liver CSCs and promote corresponding treatment strategies for HCC. From xenotransplantation and lineage tracing techniques to the current state-of-the-art single-cell sequencing technologies, advances in research tools fuel the exciting new discoveries in the field of CSCs. In particular, single-cell analysis has spearheaded a new era, with the ability to detect heterogeneity, cellular dynamics, and transition of CSCs and their progenies at a high resolution. This commentary attempts to briefly review the evolution of tools to evaluate CSCs in liver cancers, discuss their contributions and limitations, as well as their combined and complementary utilization with techniques like human tumor organoid culture. By recognizing the shortcomings of each technique, we can reassess the blind spots of CSC studies and with this knowledge, hopefully contribute to a better understanding of hepatocarcinogenesis.