Is the era of sorafenib over? A review of the literature

Hepatocellular carcinoma (HCC) is one of the most severe diseases worldwide. For the different stages of HCC, there are different clinical treatment strategies, such as surgical therapy for the early stage, and transarterial chemoembolization (TACE) and selective internal radiation therapy (SIRT) for intermediate-stage disease. Systemic treatment, which uses mainly targeted drugs, is the standard therapy against advanced HCC. Sorafenib is an important first-line therapy for advanced HCC. As a classically effective drug, sorafenib can increase overall survival markedly. However, it still has room for improvement because of the heterogeneity of HCC and acquired resistance. Scientists have reported the acquired sorafenib resistance is associated with the anomalous expression of certain genes, most of which are also related with HCC onset and development. Combining sorafenib with inhibitors targeting these genes may be an effective treatment. Combined treatment may not only overcome drug resistance, but also inhibit the expression of carcinoma-related genes. This review focuses on the current status of sorafenib in advanced HCC, summarizes the inhibitors that can combine with sorafenib in the treatment against HCC, and provides the rationale for clinical trials of sorafenib in combination with other inhibitors in HCC. The era of sorafenib in the treatment of HCC is far from over, as long as we find better methods of medication.