Molecular targeted therapy of advanced hepatocellular carcinoma beyond sorafenib.
BACKGROUND
With the recent advances in the knowledge of molecular biology of hepatocellular carcinoma (HCC), there have been encouraging developments in targeted therapy for advanced HCC.


METHODS
This review discusses the development of targeted therapy for advanced HCC patient since 2006. Among the newly identified targets, promising results have been shown in targeting the anti-angiogenic pathway. Pure anti-angiogenic agents such as bevacizumab and PTK 787 demonstrate modest activity in treating patients with advanced HCC. Sorafenib, a multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and anti-proliferative effects, has been shown to prolong the overall survival of patients with advanced HCC in two Phase III randomized trials. Like sorafenib, other anti-angiogenic multi-targeted tyrosine kinase inhibitors, such as sunitinib, pazopanib, brivanib and linifanib, also show promising activity in various stages of clinical trials. Other on-going early-phase studies are exploring the activities of drugs targeting novel pathways, such as PI3K/AKT/m TOR, hepatocyte growth factor/mesenchymal epithelial transition factor and insulin-like growth factor.


RESULTS
After reading this review, the reader should have an in-depth understanding of the latest developments in the molecular targeted therapy of advanced HCC.


CONCLUSIONS
The development of sorafenib in the treatment of advanced HCC proves the concept that molecular targeted therapies, especially anti-angiogenic agents, play a pivotal role in the treatment of this otherwise chemoresistant neoplasm. Future progress depends on further unraveling more molecular mechanisms of HCC for therapeutic intervention.
Yau
Thomas
T
The University of Hong Kong, Queen Mary Hospital, Department of Medicine, Hong Kong.
Pang
Roberta
R
Chan
Pierre
P
Poon
Ronnie T
RT
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics; D002986:Clinical Trials as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D058990:Molecular Targeted Therapy; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib