Molecular targeted therapies for cancer: sorafenib mono-therapy and its combination with other therapies (review).
Sorafenib is an oral multikinase inhibitor that acts by inhibiting tumor             growth and disrupting tumor microvasculature through antiproliferative, anti-angiogenic             and proapoptotic effects. It exerts these effects via inhibition of multiple targets             including Raf serine/threonine kinases, vascular endothelial growth factor receptor             tyrosine kinases; VEGFR-1, VEGFR-2, VEGFR-3 and platelet-derived growth factor             receptor β (PDGFR-β). Current literature shows that the deregulated signaling             through these receptors is commonly seen in human tumors. In addition, sorafenib             is also shown to induce apoptosis through downregulation of Mcl-1 in many cancer             types. Hence, sorafenib as a single agent has shown promising activity in some             cancers such as renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and             thyroid cancers. Currently, the drug holds FDA approval for the treatment of advanced             RCC and unresectable HCC. However, many clinical studies have indicated several             limitations to the application of sorafenib as a single agent in various other             cancers. Owing to these reasons and the potential of sorafenib to synergize with             other anticancer therapies, its combination with other targeted agents and chemotherapy             has been widely explored with promising results. In addition, it has also shown             synergistic results when combined with radiation. This review summarizes the current             basic and clinical studies on the effects and mechanisms of sorafenib either administered             alone or in combination with other anticancer treatments.
Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, Lowy Cancer Research Centre, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Nuha
N
Ibrahim
Yan
Y
Yu
William R
WR
Walsh
Jia-Lin
JL
Yang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib