Targeted Therapy for Hepatocellular Carcinoma: Old and New Opportunities

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver, accounting for 90% of all recorded cases. HCC is the third most common cause of cancer-related death, with a 5-year survival rate of just 3%. In the advanced stages, systemic treatments allow doctors to obtain clinical benefits, although the prognosis remains very poor. In the past few decades, new molecular targeted therapies against receptor tyrosine kinases have been developed and clinically evaluated. Sorafenib was the first oral tyrosine kinase inhibitor (TKI) approved for the treatment of advanced HCC in 2007. Subsequently, other TKIs, including Cabozantinib, Regorafenib, Lenvatinib, and vascular endothelial growth factor receptor (VEGFR) inhibitors such as Ramucirumab and VEGF inhibitors such as Bevacizumab have been approved as first- or second-line treatments. More recently, the combination of immune checkpoint inhibitors and VEGF inhibitors (Atezolizumab plus Bevacizumab) have been analyzed and approved for the treatment of advanced HCC. On the basis of the poor prognoses and the meager benefits deriving from the available systemic therapies, research into new treatments is extremely necessary. In this review, we focus on the available systemic therapies for advanced HCC, with a look toward the future.