Clinical and Biological Implications of Cancer Stem Cells in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis, and is one of the leading causes of cancer-related deaths worldwide. Recently, the development of therapeutic drugs via novel mechanisms of action, involving molecular-targeted drugs and immune checkpoint inhibitors, has progressed in the field of HCC. However, the recurrence rate remains high, and further improvement of the prognosis of patients with HCC is urgently needed. Cancer stem cells (CSCs) are a promising target for further development of novel anti-cancer drugs because they are reportedly involved in tumor initiation, maintenance, recurrence, and resistance to conventional therapies. Although several studies have already been conducted, the functions and roles of CSCs in the development and progression of tumors remain to be elucidated. In this review article, we will clarify the fundamental knowledge of CSCs necessary for the understanding of CSCs and will outline so-far identified markers specific to liver CSCs and the pathological and therapeutic implications of CSCs in HCC.