Hepatocellular carcinoma: molecular pathways and new therapeutic targets.
Hepatocellular carcinoma is often diagnosed at an advanced stage, when it is not amenable to curative therapies. There is no effective chemotherapy. Advances in cancer biology suggest that a limited number of pathways are responsible for initiating and maintaining dysregulated cell proliferation, which is the major cellular alteration responsible for the cancer phenotype. New treatments in development target several of these critical pathways, including agents targeting the receptor tyrosine kinase pathways, the Wnt/beta-catenin signaling pathway, the ubiquitin/proteasome degradation pathway, the epigenetic DNA methylation and histone deacetylation pathways, the PI3 kinase/AKT/mTOR pathway, angiogenic pathways, and telomerase. Several of these approaches hold significant promise for improving the long-term outcome of patients with advanced hepatocellular carcinoma. Because of the high prevalence of liver cirrhosis in hepatocellular carcinoma patients, these approaches must be coupled with new strategies for halting or reversing the progression of chronic liver disease.
Roberts
Lewis R
LR
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55902, USA.
Gores
Gregory J
GJ
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic; D019175:DNA Methylation; D004195:Disease Models, Animal; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000097782:NF-kappaB-Inducing Kinase
D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D000097782:NF-kappaB-Inducing Kinase; C494918:AKT1 protein, human