Tyrosine kinase inhibitors to treat liver cancer.
BACKGROUND
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Although patients with early-stage disease have a good prognosis, there has been no effective therapy available for those with advanced disease. Despite the death risk of patients with advanced HCC being reduced with sorafenib therapy, many patients eventually turn out to be refractory to this therapy. Thus, treatment of HCC remains an urgent health concern.


METHODS
Recent improvement in understanding the pathophysiology of HCC at the molecular level has fostered the development of molecular targeted therapies that specifically block the disrupted pathways.


RESULTS
This review summarizes the preclinical and clinical data from 2004 to 2009 on the efficacy and safety of the emerging drug for the treatment of HCC, including small molecule inhibitors (erlotinib, sunitinib, sorafenib, vandetanib, cediranib, brivanib and dovitinib) and the rationale for combination therapies for patients with advanced HCC.


CONCLUSIONS
Understanding the mechanisms of action, safety and efficacy of these new agents and new methods of combining these drugs may help prolong overall survival of patients with HCC and reduce disease recurrence after surgery or ablative therapies.
National Cancer Centre of Singapore, Humphrey Oei Institute of Cancer Research, Division of Cellular and Molecular Research, Laboratory of Molecular Endocrinology, 11 Hospital Drive, 169610, Singapore. cmrhth@nccs.com.sg
Hung
H
Huynh
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000453:epidemiology; D016503:Drug Delivery Systems / Q000379:methods*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
D015507:Drugs, Investigational; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases