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 tumorgrowth and disrupting tumor microvasculature through antiproliferative, anti-angiogenicand proapoptotic effects. It exerts these effects via inhibition of multiple targetsincluding Raf serine/threonine kinases, vascular endothelial growth factor receptortyrosine kinases; VEGFR-1, VEGFR-2, VEGFR-3 and platelet-derived growth factorreceptor β (PDGFR-β). Current literature shows that the deregulated signalingthrough these receptors is commonly seen in human tumors. In addition, sorafenibis also shown to induce apoptosis through downregulation of Mcl-1 in many cancertypes. Hence, sorafenib as a single agent has shown promising activity in somecancers such as renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) andthyroid cancers. Currently, the drug holds FDA approval for the treatment of advancedRCC and unresectable HCC. However, many clinical studies have indicated severallimitations to the application of sorafenib as a single agent in various othercancers. Owing to these reasons and the potential of sorafenib to synergize withother anticancer therapies, its combination with other targeted agents and chemotherapyhas been widely explored with promising results. In addition, it has also shownsynergistic results when combined with radiation. This review summarizes the currentbasic and clinical studies on the effects and mechanisms of sorafenib either administeredalone or in combination with other anticancer treatments.