Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Unit 1362, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Recent Pat Anticancer Drug Discov. 2012 Jan;7(1):14-30. doi: 10.2174/157489212798357930.
The insulin-like growth factor (IGF) family and the IGF-1 receptor (IGF-1R) play an important role in cancer. This intricate and complex signaling pathway provides many opportunities for therapeutic intervention, and several novel therapeutics aimed at the IGF-1R, particularly monoclonal antibodies and small molecule tyrosine kinase inhibitors, are under clinical investigation. This article provides a patent overview of the IGF signaling pathway and its complexity, addresses the justification for the use of IGF-1R-targeted therapy, and reviews the results of in vivo and in vitro novel therapeutics. Over the past year, the completion of several phase I, II, and III trials have provided interesting new information about the clinical activity of these novel compounds, particularly CP-751,871, IMC-A12, R1507, AMG-479, AVE-1642, MK-0646, XL-228, OSI-906, and BMS-754807. We review the important preliminary results from clinical trials with these compounds and conclude with a discussion about future therapeutic efforts.
胰岛素样生长因子 (IGF) 家族和 IGF-1 受体 (IGF-1R) 在癌症中发挥着重要作用。这一错综复杂的信号通路为治疗干预提供了许多机会，几种针对 IGF-1R 的新型治疗药物，特别是单克隆抗体和小分子酪氨酸激酶抑制剂，正在进行临床研究。本文对 IGF 信号通路及其复杂性进行了专利概述，阐述了使用 IGF-1R 靶向治疗的合理性，并回顾了新型治疗药物的体内和体外研究结果。在过去的一年中，完成的几项 I、II 和 III 期临床试验提供了有关这些新型化合物临床活性的有趣新信息，特别是 CP-751,871、IMC-A12、R1507、AMG-479、AVE-1642、MK-0646、XL-228、OSI-906 和 BMS-754807。我们回顾了这些化合物临床试验的重要初步结果，并对未来的治疗努力进行了讨论。
