The team found that disulfiram acts as a copper ionophore to downregulate an RNA methylase called TRMT10C. This reduction in TRMT10C activity decreases methylation on the mRNA of c-FOS, a transcription factor, leading to its increased expression. Elevated c-FOS then suppresses two critical downstream targets: PCSK9 (involved in lipid metabolism) and CD146 (a promoter of angiogenesis).
Experiments in cell lines and mouse models showed that disulfiram alone - or in combination with the anti-angiogenic drug thalidomide - significantly inhibited tumor growth, reduced lipid droplet accumulation, and blocked new blood vessel formation. Clinical data from HCC patients further supported the relevance of this pathway: high TRMT10C and PCSK9 expression correlated with poor prognosis, while high c-FOS was associated with better survival.
“Our findings reveal a previously unknown mechanism by which disulfiram combats liver cancer through RNA epigenetic regulation,” said corresponding author Jinglin Xia. “This not only provides a new therapeutic strategy but also supports drug repurposing as a viable approach in oncology.”
Qi Z, Kong X, Wu J, Du X, Jiang M, Yu Z, Shen X, Fang Y, Xia J.
Disulfiram-induced c-FOS influences lipid metabolism and angiogenesis in hepatocellular carcinoma.
Sci China Life Sci. 2026 Feb;69(2):455-472. doi: 10.1007/s11427-024-2968-1