Hepatocellular carcinoma (HCC) is the third cause of cancer-related death and accounts for more than 90% of primary liver cancers. It is most frequently diagnosed at an advanced stage in patients with chronic liver injury and cirrhosis. Despite dedicated research in the last few decades, significant advancements in the treatment of HCC have not been achieved, and HCC still belongs to the category of cancers with a very low 5-year survival rate of less than 20%.
The main risk factors for HCC are chronic hepatitis B and C virus infections and obesity and metabolic syndrome. Alcoholic liver disease, steatohepatitis, alfatoxins, and hemochromatosis have also been recognized to contribute to HCC development.
Treatment of HCC is hindered by a high rate of advanced stage diagnosis and lack of therapeutic options for advanced disease. Approximately 40% of HCC cases are diagnosed at an advanced stage when radical treatment approaches, including surgery and liver transplantation, are no longer available. Therefore, systemic therapy with an oral targeted multikinase inhibitor, sorafenib, is the treatment of choice for patients presenting with advanced disease where tumor has spread beyond the liver. Treatment of advanced HCC is especially challenging because of a high rate of drug resistance and underlying liver dysfunction that affects drug delivery and distribution.