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Figure 2. Key features of liver cancer stem cells (CSCs). Liver CSCs present some common key functional features. CSCs represent a peculiar sub-compartment of tumor cells crucially involved in drug resistance. Current therapeutic strategies for the treatment of hepatic cancer mostly focus on the inhibition of tumor growth, resulting in the death of only bulk tumor cells. CSCs are able to survive thanks to intrinsic and extrinsic mechanisms of chemo-resistance and subsequently they can give rise to primary liver cancer recurrence. Moreover, CSCs are the only cells endowed with metastatic potential. While mature tumor cells mostly die through natural apoptosis into blood circulation, CSCs, however, have a significantly higher viability, enhanced homing ability into the bloodstream as circulating CSCs as well as higher distant metastasis initiation capability. Next, CSCs are characterized by metabolic changes, but, no consensus has been reached on the metabolic features of CSCs, which are very plastic and so able to modify their metabolic features according to specific needs. Then, CSCs can exhibit enhanced glycolytic activity as well as increased mitochondrial oxidative phosphorylation (OXPHOS) with subsequent increased fatty acid oxidation, depending on tumor context. All these features make CSCs particularly hard to eradicate. FAO: fatty acid oxidation