Quantitative phosphoproteomic analysis identifies the potential therapeutic target EphA2 for overcoming sorafenib resistance in hepatocellular carcinoma cells

Liver cancer: A new route to fighting drug resistance Inhibiting the activity of a protein known as EphA2 may help overcome the development of drug resistance during treatment of hepatocellular carcinoma, the most common form of liver cancer. Resistance often develops to sorafenib, the main drug treatment option for the advanced disease. Researchers in Taiwan led by Lu-Ping Chow at the National Taiwan University in Taipei investigated the role of around 1500 phosphoproteins, which are regulated by the attachment and removal of small chemical groups containing phosphorus and oxygen. The activity of the phosphoprotein EphA2 was identified as a major contributor to drug resistance. This was linked to the ability of EphA2 to interfere with a molecular signaling pathway previously implicated in sorafenib activity. Suppressing EphA2 activity suppressed the development of sorafenib resistance in cultured cells and in mice with liver cancer, suggesting therapeutic possibilities.