Role of metabolism in sorafenib-resistance hepatocellular carcinoma cellular model.

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer and the third leading cause of cancer-related deaths worldwide. Potentially curative treatment of HCC involves various possibilities based on the stage of the disease. For the advanced stage of this disease, sorafenib is one of the first-line treatment options. It is an oral tyrosine kinase inhibitor, targeting several signalling pathways involved in tumor growth and angiogenesis.However, its usage is limited because many patients develop resistance after a short period (six months) of treatment. Hepatoblasts knock-out for p53, and overexpressing Myconcogene(p53-/-; Myc) are used to reproduce the genetic settings of HCCin vitroand are treated with sorafenib attwo different time points: short (48 hours) and long (7 days) exposure. Thecombination oftranscriptomic and metabolomicdata was utilizedto unravel the effect of this drug on cellular metabolism and mitochondrial function,with the final aim of increasing the effectiveness of sorafenibtreatment.