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.
Oncol Rep. 2012 May;27(5):1303-11. doi: 10.3892/or.2012.1675. Epub 2012 Feb 6.
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.
索拉非尼是一种口服多激酶抑制剂，通过抗增殖、抗血管生成和促凋亡作用来抑制肿瘤生长和破坏肿瘤微血管。它通过抑制多种靶点来发挥这些作用，包括 Raf 丝氨酸/苏氨酸激酶、血管内皮生长因子受体酪氨酸激酶；VEGFR-1、VEGFR-2、VEGFR-3 和血小板衍生生长因子受体β（PDGFR-β）。目前的文献表明，这些受体的失调信号在人类肿瘤中很常见。此外，索拉非尼还通过下调许多癌症类型中的 Mcl-1 诱导细胞凋亡。因此，索拉非尼作为单一药物在某些癌症中显示出有希望的活性，如肾细胞癌（RCC）、肝细胞癌（HCC）和甲状腺癌。目前，该药物已获得 FDA 批准用于治疗晚期 RCC 和不可切除的 HCC。然而，许多临床研究表明，索拉非尼作为单一药物在各种其他癌症中的应用存在一些局限性。由于这些原因以及索拉非尼与其他抗癌疗法协同增效的潜力，它与其他靶向药物和化疗的联合应用得到了广泛的探索，并取得了有希望的结果。此外，它与放射治疗联合使用也显示出协同作用。这篇综述总结了目前关于索拉非尼单独或联合其他抗癌治疗的作用和机制的基础和临床研究。
