Steeghs Neeltje, Nortier Johan W R, Gelderblom Hans
Department of Clinical Oncology K1-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Ann Surg Oncol. 2007 Feb;14(2):942-53. doi: 10.1245/s10434-006-9227-1. Epub 2006 Nov 14.
Small molecule tyrosine kinase inhibitors (TKIs) are developed to block intracellular signaling pathways in tumor cells, leading to deregulation of key cell functions such as proliferation and differentiation. Over 25 years ago, tyrosine kinases were found to function as oncogenes in animal carcinogenesis; however, only recently TKIs were introduced as anti cancer drugs in human cancer treatment. Tyrosine kinase inhibitors have numerous good qualities. First, in many tumor types they tend to stabilize tumor progression and may create a chronic disease state which is no longer immediately life threatening. Second, side effects are minimal when compared to conventional chemotherapeutic agents. Third, synergistic effects are seen in vitro when TKIs are combined with radiotherapy and/or conventional chemotherapeutic agents. In this article, we will give an update of the tyrosine kinase inhibitors that are currently registered for use or in an advanced stage of development, and we will discuss the future role of TKIs in the treatment of solid tumors. The following TKIs are reviewed: Imatinib (Gleevec/Glivec), Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva), Lapatinib (GW-572016, Tykerb), Canertinib (CI-1033), Sunitinib (SU 11248, Sutent), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava).
小分子酪氨酸激酶抑制剂（TKIs）旨在阻断肿瘤细胞内的信号通路，从而导致关键细胞功能（如增殖和分化）失调。25年多前，酪氨酸激酶被发现作为癌基因在动物致癌过程中发挥作用；然而，直到最近TKIs才作为抗癌药物被引入人类癌症治疗。酪氨酸激酶抑制剂具有许多优良特性。首先，在许多肿瘤类型中，它们往往能稳定肿瘤进展，并可能形成一种不再立即危及生命的慢性病状态。其次，与传统化疗药物相比，其副作用极小。第三，当TKIs与放疗和/或传统化疗药物联合使用时，在体外可见协同效应。在本文中，我们将介绍目前已注册使用或处于开发后期的酪氨酸激酶抑制剂的最新情况，并讨论TKIs在实体瘤治疗中的未来作用。以下TKIs将被综述：伊马替尼（格列卫/格列宁）、吉非替尼（易瑞沙）、厄洛替尼（OSI-774，特罗凯）、拉帕替尼（GW-572016，泰立沙）、卡奈替尼（CI-1033）、舒尼替尼（SU 11248，索坦）、扎西他滨（ZD6474）、凡他尼布（PTK787/ZK 222584）、索拉非尼（拜耳43-9006，多吉美）和来氟米特（SU101，爱若华）。
