New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical...

Area of Science:

• Hepatocellular carcinoma (HCC) research
• Molecular oncology
• Drug development

Background:

• Advanced hepatocellular carcinoma (HCC) presents a lethal threat due to its aggressive nature and limited effective systemic treatments.
• Sorafenib is the sole systemic therapy offering an overall survival benefit for advanced HCC, highlighting the urgent need for novel therapeutic agents.
• The complex molecular pathways driving HCC oncogenesis, proliferation, and survival present numerous targets for developing molecularly targeted therapies.

Purpose of the Study:

• To evaluate molecular agents targeting pathogenic pathways in advanced hepatocellular carcinoma (HCC).
• To review recently completed and ongoing phase III drug studies of molecularly targeted agents in advanced HCC.
• To provide a brief description of the biologic rationale underpinning these targeted agents.

Main Methods:

• Review of completed and ongoing phase III clinical trials for advanced HCC.
• Analysis of molecularly targeted agents, including those targeting angiogenesis and cancer cell-directed oncogenic signaling.
• Examination of agents targeting vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-mesenchymal-epithelial transition factor-1, and mammalian target of rapamycin signaling.

Main Results:

• Completed phase III studies involved agents such as sorafenib, sunitinib, brivanib, linifanib, erlotinib, everolimus, ramucirumab, and orantinib.
• Ongoing phase III studies are investigating agents including lenvatinib, regorafenib, tivantinib, and cabozantinib.
• The evaluation encompasses a range of molecular targets and their application in advanced HCC treatment.

Conclusions:

• Molecularly targeted therapies offer promising avenues for treating advanced hepatocellular carcinoma (HCC).
• Continued research and clinical trials are essential to identify and validate new agents for improved patient outcomes.
• Understanding the biologic rationale behind these agents is critical for their effective clinical application in HCC management.