Molecular targeted therapy for hepatocellular carcinoma: current and future

Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide. The majority of HCC cases occur in patients with chronic liver disease. Despite regular surveillance to detect small HCC in these patients, HCC is often diagnosed at an advanced stage. Because HCC is highly resistant to conventional systemic therapies, the prognosis for advanced HCC patients remains poor. The introduction of sorafenib as the standard systemic therapy has unveiled a new direction for future research regarding HCC treatment. However, given the limited efficacy of the drug, a need exists to look beyond sorafenib. Many molecular targeted agents that inhibit different pathways involved in hepatocarcinogenesis are under various phases of clinical development, and novel targets are being assessed in HCC. This review aims to summarize the efforts to target molecular components of the signaling pathways that are responsible for the development and progression of HCC and to discuss perspectives on the future direction of research.

Keywords: Hepatocellular carcinoma; Molecular agents; Sorafenib; Targeted therapy.

Figure 1

Ras/Raf/MEK/ERK signaling pathways and molecular targeted agents which is currently available or in development for hepatocellular carcinoma. EGF: Epidermal growth factor; EGFR: EGF receptor; ERK: Extracellular signal-regulated kinase; FGFR: Fibroblast growth factor receptor; IGFR: Insulin-like growth factor receptor; PDGFR: Platelet-derived growth factor receptor; VEGF: Vascular endothelial growth factor; VEGFR: VEGF receptor; MEK: Mitogen/extracellular protein kinase.

Figure 2

PI3K/Akt/mTOR pathway and the molecular agents targeting this pathway. BAD: BCL-2-associated death promoter; EGF: Epidermal growth factor; EGFR: EGF receptor; IGFR: Insulin-like growth factor (IGF) receptor; mTOR: Mammalian target of rapamycin; PTEN: Phosphatase and tensin homolog; PI3K: Phosphatidylinositol-3-kinase.