Liver tumor cells do not respond to sorafenib if they have a less differentiated phenotype, known as the mesenchymal type, and express CD44, according to a new study. These findings, from work in liver cell tumor lines and mice, could serve to select patients with hepatocellular carcinoma unresponsive to sorafenib, which is the most frequently used drug in liver cancer.

Hepatocellular carcinoma is a cancer with a poor prognosis and more difficult treatment. Surgery is only possible when the tumor is well located. The protocol for liver transplantation requires specific requirements for number and size of tumor nodules.

However, advanced stages of hepatocellular carcinoma can be treated with sorafenib. It is a tyrosine kinase inhibitor that has an extremely specific action.

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“Sorafenib could act not only on tumor cells by inhibiting the growth and inducing cell death but also on cells accompanying the tumor, the stroma, by their ability to inhibit the formation of blood vessels to provide nutrients to the tumor cells. Sorafenib treatment induces a delay in tumor process but generally fails to produce the patient’s recovery,” explained lead study researcher Isabel Fabregat, PhD, of the Institute of Biomedical Research in Barcelona, Spain.

Many laboratories are currently studying the action of sorafenib to improve therapy by either attaching different drugs or selecting patients. This study, published in the International Journal of Cancer (2014; doi:10.1002/ijc.29097), analyzed the phenotypic and molecular characteristics of several cell lines and their response to sorafenib. They also examined how animal models responded to sorafenib.

“We have observed that the cells that exhibit a mesenchymal phenotype, where the tumor cells are less differentiated and are potentially more aggressive, and that express CD44, a marker of tumor-initiating cells, are resistant to sorafenib,” said Fabregat.

The study proposes CD44 as a potential marker that could be used clinically to select patients who will not respond to treatment and thus spare them the side effects. Fabregat also explained that the study opens the door to designing joint therapies with sorafenib and CD44 inhibitors.