Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSCs) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSCs play a central role in tumor development, metastasis, and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSCs have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSCs has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSCs. Although inhibitors of CSCs show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSCs are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology.