Evolving role of Sorafenib in the management of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide and comes third in cancer-related mortality. Although there is a broad spectrum of treatment options to choose from, only a few patients are eligible candidates to receive a curative therapy according to their stage of disease, and thus palliative treatment is implemented in the majority of the patients suffering from liver cancer. Sorafenib, a multikinase inhibitor, is the only currently approved agent for systemic therapy in patients with advanced stage HCC and early stage liver disease. It has been shown to improve the overall survival, but with various side effects, while its cost is not negligible. Sorafenib has been in the market for a decade and has set the stage for personalized targeted therapy. Its role during this time has ranged from monotherapy to neoadjuvant and adjuvant treatment with surgical resection, liver transplantation and chemoembolization or even in combination with other chemotherapeutic agents. In this review our aim is to highlight in depth the current position of Sorafenib in the armamentarium against HCC and how that has evolved over time in its use either as a single agent or in combination with other therapies.

Keywords: Adjuvant therapy; Hepatocellular carcinoma; Liver cancer; Liver neoplasm; Liver resection; Liver transplantation; Multikinase inhibitor; Signaling pathways; Sorafenib; Targeted therapy; Tumor angiogenesis.

Figure 1

Sorafenib’s mechanism of action. In tumor cells sorafenib blocks the Raf/MEK/ERK cascade and can lead to apoptosis through various mechanisms, such as inhibition of eukaryotic translation initiation factor 4E phosphorylation. In vascular endothelial cells, it inhibits receptor tyrosine kinases, such as VEGFR and PDGFR. PDGFR: Platelet-derived growth factor receptor; VEGFR: Vascular endothelial growth factor receptor.

Figure 2

Barcelona clinic liver cancer staging system and treatment algorithm. PS: Performance status; N: Nodules; M: Metastases; HCC: Hepatocellular carcinoma.