title: Sorafenib-based combined molecule targeting in treatment of hepatocellular carcinoma.
abstract: Sorafenib is the only and standard systematic chemotherapy drug for treatment of advanced hepatocellular carcinoma (HCC) at the current stage. Although sorafenib showed survival benefits in large randomized phase III studies, its clinical benefits remain modest and most often consist of temporary tumor stabilization, indicating that more effective first-line treatment regimens or second-line salvage therapies are required. The molecular pathogenesis of HCC is very complex, involving hyperactivated signal transduction pathways such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR and aberrant expression of molecules such as receptor tyrosine kinases and histone deacetylases. Simultaneous or sequential abrogation of these critical pathways or the functions of these key molecules involved in angiogenesis, proliferation, and apoptosis may yield major improvements in the management of HCC. In this review, we summarize the emerging sorafenib-based combined molecule targeting for HCC treatment and analyze the rationales of these combinations.
authors.affiliation: Jian-Jun Gao, Zhen-Yan Shi, Department of Pharmacology, School of Pharmaceutical Sciences, Qingdao University, Qingdao 266021, Shandong Province, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Gao
authors.affiliation: Jian-Jun Gao, Zhen-Yan Shi, Department of Pharmacology, School of Pharmaceutical Sciences, Qingdao University, Qingdao 266021, Shandong Province, China.
authors.forename: Zhen-Yan
authors.initials: ZY
authors.lastname: Shi
authors.affiliation: Jian-Jun Gao, Zhen-Yan Shi, Department of Pharmacology, School of Pharmaceutical Sciences, Qingdao University, Qingdao 266021, Shandong Province, China.
authors.forename: Ju-Feng
authors.initials: JF
authors.lastname: Xia
authors.affiliation: Jian-Jun Gao, Zhen-Yan Shi, Department of Pharmacology, School of Pharmaceutical Sciences, Qingdao University, Qingdao 266021, Shandong Province, China.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Inagaki
authors.affiliation: Jian-Jun Gao, Zhen-Yan Shi, Department of Pharmacology, School of Pharmaceutical Sciences, Qingdao University, Qingdao 266021, Shandong Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D058990:Molecular Targeted Therapy; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D056572:Histone Deacetylase Inhibitors; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: Angiogenesis; Endothelial growth factor receptor; Extracellular-signal regulated kinase; Histone deacetylases; Mammalian target of rapamycin