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

Abstract

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.

Crosstalk between Macrophages, T Cells, and Iron Metabolism in Tumor Microenvironment

“…In fact, cisplatin, a classic chemotherapy agent, was found to induce ferroptosis through glutathione deletion in certain cancer cell lines [ 165 ]. Sorafenib is a multikinase inhibitor approved for the treatment of advanced cancer (e.g., hepatocellular carcinoma) [ 166 ], and it can be used as an agonist of ferroptosis for its inhibitory effect on system xc- [ 167 ]. More importantly, erastin, a more potent inhibitor of system xc-, has been shown to improve the anticancer activity of traditional chemotherapy drugs (e.g., docetaxel, cisplatin, and temozolomide) in several cancer cells [ 168 – 170 ].…”

Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment

“…At an early stage of the disease, HCC can be treated by surgical resection, percutaneous ablation, or liver transplantation. At a later stage, the therapeutic options have been limited during the last decade to Sorafenib (a multikinase inhibitor) [ 7 , 8 ]. Recently, other first-line treatments such as lenvatinib and second-line treatments such as regorafenib and cabozantinib have been proposed for treatment.…”

AG-1024 Sensitizes Sorafenib-Resistant Hepatocellular Carcinoma Cells to Sorafenib via Enhancing G1/S Arrest

“…As an inhibitor targeting multiple tyrosine protein kinases (VEGFR, PDGFR and Raf family kinases), sorafenib acts on numerous targets to inhibit cancer proliferation and tumor angiogenesis, which can effectively lead to a decrease in mortality in HCC patients. 18 , 19 Advanced stage HCC patients can benefit from 400mg twice daily sorafenib therapy. 5 , 6 , 20 To date, however, clinical trials have revealed that only about 30% patients show sensitivity to sorafenib, and HCC usually progresses within 6 months resulting from resistance to sorafenib.…”