Understanding how hypoxia contributes to liver cancer stem cells maintenance

It is widely believed that the existence of cancer stem cells (CSCs) is a crucial factor leading to treatment failure and tumor recurrence in hepatocellular carcinoma (HCC). Therefore, targeted therapy for CSCs has become a novel strategy for solving tumor treatment resistance and recurrence. Accumulating evidence supports the presence of a dynamic CSC-niche interplay that regulates the properties of liver CSCs. The hypoxic microenvironment within tumors probably favors the maintenance of stemness in CSCs. Many studies have shown that hypoxic regions are easily formed at various stages of HCC treatment. Therefore, it is necessary to elucidate the mechanisms by which the hypoxic environment in HCC regulates the stemness of liver CSCs. In this review, we summarized the potential factors contributing to the formation of hypoxic regions in the development and treatment of HCC. We focused on changes in the CSC niche mediated by hypoxia. We also highlighted the potential mechanisms by which HCC cells acquire CSC properties in a hypoxic microenvironment. And we summarize the current research-based targeted therapeutic strategies based on the hypoxic microenvironment.