Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma

Alpha-foetoprotein (AFP), one of the first protein tumour markers discovered, is widely used today in clinical practice. Its application for the screening and diagnosis of hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour, is a matter of extensive debate. In addition to the studies focused on the role of the AFP in the diagnosis of HCC, in recent years AFP has been used to guide the therapeutic choice in HCC and monitor the treatment. Here, we summarize the latest studies that show the interest of AFP quantification in determining the suitability of liver transplantation or to follow-up on patients receiving the targeted treatment sorafenib. We also highlight the recent studies showing the active role of AFP in tumour progression, and the new modes of regulation of this tumour marker. Among these is the regulation of AFP through tumour proteostasis and the Unfolded Protein Response (UPR). We discuss the implications of this new knowledge in the therapeutic context, in terms of interpreting serum levels of AFP, and the new perspectives offered by AFP for the study of tumour proteostasis. •AFP status defines a subset of HCC with particular biological properties.•AFP may play an active role in hepatocarcinogenesis.•The Unfolded Protein Response (UPR) regulates AFP production.•Serum levels of AFP might reflect tumour proteostasis in the therapeutic context.