The multikinase inhibitor sorafenib induces p53 family-dependent apoptosis in hepatocellular carcinoma

The multikinase inhibitor sorafenib represents the first medical therapy to prolong survival of patients suffering from hepatocellular carcinoma. Here, we propose a new model of action for sorafenib via accumulation and activation of p53 and its family members p63 and p73. We have previously linked the p53 family to hepatocarcinogenesis, chemosensitivity and prognosis in hepatocellular carcinoma. Here, we show that sorafenib-induced apoptosis is p53-family-dependent and associated with classical downstream effects of this gene family. Blocking p53 family function using an siRNA approach leads to a substantial de…