A study led by Isabel Fabregat from the Institute of Biomedical Research and the University of Barcelona (both Spain), holds the potential to select patients with hepatocellular carcinoma who are unresponsive to the most frequently used drug for liver cancer, sorafenib.
This study, published in the International Journal of Cancer, describes how tumor cells with a less differentiated phenotype and that express CD44 do not respond to sorafenib action.
Patients diagnosed with hepatocellular carcinoma have poor prognoses. Treatment is difficult, with surgery only possible when the tumor is well located and the protocol for liver transplantation requires specific conditions. However, the tyrosine kinase inhibitor sorafenib can be utilized, to limited success, as explained by Fabregat: “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.”
A number of groups are currently studying the action of this drug and working to improve therapy through either the attachment of different drugs or patient selection. In the present study, CD44 is proposed as a potential marker for clinical use for the selection of patients who will not respond to treatment, thus sparing them adverse effects.
“We have observed that the cells which exhibit a mesenchymal phenotype (where the tumor cells are less differentiated and are potentially more aggressive) and which express CD44, a marker of tumor-initiating cells, are resistant to sorafenib”, explained Fabregat.”Moreover,” she concluded, “the proposal of this paper is twofold. It also opens the door to designing joint therapies with sorafenib and CD44 inhibitors as we have shown that genetic inhibition of this marker in resistant cell lines to sorafenib makes them sensitive.”
Sources: Fernando J, Malfettone A, Cepeda EB, et al. A mesenchymal-like Phenotype and expression of CD44 PREDICT lack of apoptótica response to sorafenib in liver tumor cells. Int. J. Cancer. doi:10.1002/ijc.29097 (2014) [Epub ahead of print]; Institute of Biomedical Research press release