Phytochemicals to Target Sorafenib Resistance Pathways in Liver Cancer

Hepatocellular carcinoma (HCC) is the primary form of liver cancer. With more than 70% of liver cancer cases identified as HCC, it is ranked second in terms of cancer-related mortality across the world. Viral infections such as hepatitis B and C, cirrhosis, are the dominant factors for the causation of this deadly disease. With the etiology of the disease changing every year due to factors like lifestyle changes and increased exposure to factors like alcohol, the epidemiology of HCC is morphing continuously limiting the available diagnosis and treatment options. Sorafenib is a multi-kinase inhibitor approved for HCC treatment by the FDA since 2007. Also used as a first-line treatment for renal cell carcinoma, this chemotherapeutic agent has previously been shown to increase the median survival expectancy in patients with advanced HCC. However, the increase in the side effects and resistance against the drug has pivoted researchers from across the globe to find alternatives from natural sources such as phytochemicals. This interactive book chapter discusses the details of sorafenib as a therapeutic target to treat HCC, its mode of action, modes and mechanisms of sorafenib resistance in HCC patients, and the advances in the field of phytochemical research to overcome sorafenib resistance in liver cancer.