Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for over 90% of all cases. Patients with advanced-stage HCC are referred to systemic treatment. Although some advances in HCC therapy have been made in recent years, the prognosis for patients remains poor due to drug resistance, tumor relapse, and metastasis, implying that overall survival remains a challenge. Many studies have shown that tumor-initiating stem cells, also known as cancer stem cells (CSCs), play essential roles in tumorigenesis, metastasis, and treatment resistance in HCC and that future cancer treatments could be significantly improved by targeting this cell population subset. Different markers of CSCs from HCC have been identified, and intracellular signaling pathways and extracellular factors have been reported as targets capable of removing this cell subpopulation, highlighting the possibility of developing targeted drugs to eradicate HCC CSCs. In this review, we highlight emerging small compounds that target HCC CSCs to provide new insights and guide future research. Drugs in the preclinical and clinical trial development stages were selected and discussed.