Int J Biol Sci 2022; 18(2):536-551. doi:10.7150/ijbs.64537 This issue

Review

The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We?

Xin Hu1,2,3,*, Ronggao Chen3,*, Qiang Wei1, Xiao Xu1,2,3,4✉

1. Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
2. Zhejiang University Cancer Center, Hangzhou, 310058, China.
3. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
4. Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.
* These authors contributed equally to this work.

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Citation:
Hu X, Chen R, Wei Q, Xu X. The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We?. Int J Biol Sci 2022; 18(2):536-551. doi:10.7150/ijbs.64537. Available from https://www.ijbs.com/v18p0536.htm

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Abstract

Graphic abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has been acknowledged as a leading cause of death among cirrhosis patients. Difficulties in early diagnosis and heterogeneity are obstacles to effective treatment, especially for advanced HCC. Liver transplantation (LT) is considered the best therapy for HCC. Although many biomarkers are being proposed, alpha-fetoprotein (AFP), which was identified over 60 years ago, remains the most utilized. Recently, much hope has been placed in the immunogenicity of AFP to develop novel therapies, such as AFP vaccines and AFP-specific adoptive T-cell transfer (ACT). This review summarizes the performance of AFP as a biomarker for HCC diagnosis and prognosis, as well as its correlation with molecular classes. In addition, the role of AFP in LT is also described. Finally, we highlight the mechanism and application prospects of two immune therapies (AFP vaccine and ACT) for HCC. In general, our review points out the prevalence of AFP in HCC, accompanied by some controversies and novel directions for future research.

Keywords: Alpha-fetoprotein, Hepatocellular carcinoma, Liver transplantation, Chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor-engineered T-cell therapy