Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies

Author:

Wang Nuozhou1,Wang Shanshan2,Li Ming-Yue34,Hu Bao-guang5,Liu Li-ping6,Yang Sheng-li7,Yang Shucai8,Gong Zhongqin1,Lai Paul B. S.1,Chen George G.14

Affiliation:

1. Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China

2. Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China

3. Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China

4. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China

5. Department of Gastrointestinal Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China

6. Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong Province, China

7. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

8. Department of Clinical Laboratory, Pingshan District People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, China

Abstract

The poor clinical outcome of hepatocellular carcinoma (HCC) patients is ascribed to the resistance of HCC cells to traditional treatments and tumor recurrence after curative therapies. Cancer stem cells (CSCs) have been identified as a small subset of cancer cells which have high capacity for self-renewal, differentiation and tumorigenesis. Recent advances in the field of liver CSCs (LCSCs) have enabled the identification of CSC surface markers and the isolation of CSC subpopulations from HCC cells. Given their central role in cancer initiation, metastasis, recurrence and therapeutic resistance, LCSCs constitute a therapeutic opportunity to achieve cure and prevent relapse of HCC. Thus, it is necessary to develop therapeutic strategies to selectively and efficiently target LCSCs. Small molecular inhibitors targeting the core stemness signaling pathways have been actively pursued and evaluated in preclinical and clinical studies. Other alternative therapeutic strategies include targeting LCSC surface markers, interrupting the CSC microenvironment, and altering the epigenetic state. In this review, we summarize the properties of CSCs in HCC and discuss novel therapeutic strategies that can be used to target LCSCs.

Funder

Research Grants Council, University Grants Committee

National Natural Science Foundation of China

CUHK Direct Grant

Publisher

SAGE Publications

Subject

Oncology

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