Biomarkers of apoptosis and necrosis in patients with hepatocellular carcinoma treated with sorafenib

Abstract

Background/aim: Sorafenib is the medical reference for treatment of hepatocellular carcinoma (HCC). Multiple forms of cytotoxicity are induced by sorafenib in HCC cells in vitro but it is unclear what extent of apoptosis and necrosis is induced in HCC patients receiving sorafenib.

Patients and methods: The M30 and M65 biomarkers, which reflect the release of cytokeratin-18 and its apoptotic cleavage fragments, were measured in patients with HCC (n=36) and matched patients with cirrhosis (n=47). A serum sample was collected from 20 patients with HCC four weeks after the onset of treatment with sorafenib.

Results: Basal serum levels of M30 and M65 were increased in patients with HCC compared to those with uncomplicated cirrhosis. No statistically significant increase in the level of M30 or M65 was found in the sera of patients with HCC after sorafenib.

Conclusion: The findings indicate that sorafenib is not a potent inducer of HCC cell death in most patients.

Keywords: Hepatocellular carcinoma; M30; M65; programmed cell death; sorafenib.