Department of Clinical and Biological Sciences, Thoracic Oncology Unit, University of Turin, S. Luigi Hospital, Orbassano, Italy.
Cancer Treat Rev. 2012 Jun;38(4):292-302. doi: 10.1016/j.ctrv.2011.07.008. Epub 2011 Sep 9.
The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have become increasingly recognized as having a driving role in the development of malignancy, and consequently IGF-1R has become a potential target for cancer therapy. Several inhibitors of IGF-1R are in clinical development for the treatment of solid tumors, including non-small cell lung cancer (NSCLC). These IGF-1R-targeted agents include monoclonal antibodies such as cixutumumab (IMC-A12), AMG-479, AVE1642, BIIB022, dalotuzumab (MK-0646), and robatumumab (Sch717454), the ligand neutralizing antibody Medi-573, and the small molecule inhibitors BMS-754807, linsitinib (OSI-906), XL228, and AXL1717. Two phase III trials of the anti-IGF-1R monoclonal antibody, figitumumab (CP-751,871), were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints. In light of disappointing clinical data with figitumumab and other targeted agents, it is likely that the use of molecular markers will become important in predicting response to treatment. This review outlines the role of IGF-1R signaling in solid tumors with a particular focus on NSCLC, and provides an overview of clinical data.
1 型胰岛素样生长因子受体 (IGF-1R) 及其下游信号成分在恶性肿瘤的发展中越来越被认为具有驱动作用，因此 IGF-1R 已成为癌症治疗的潜在靶点。几种 IGF-1R 抑制剂正在开发用于治疗实体瘤，包括非小细胞肺癌 (NSCLC)。这些针对 IGF-1R 的药物包括单克隆抗体，如 cixutumumab (IMC-A12)、AMG-479、AVE1642、BIIB022、dalotuzumab (MK-0646) 和 robatumumab (Sch717454)、配体中和抗体 Medi-573 以及小分子抑制剂 BMS-754807、linsitinib (OSI-906)、XL228 和 AXL1717。两种针对 IGF-1R 单克隆抗体 figitumumab (CP-751,871) 的 III 期试验于 2010 年停止，因为认为这两项试验都不太可能达到其主要终点。鉴于 figitumumab 和其他靶向药物的令人失望的临床数据，使用分子标志物预测治疗反应可能变得非常重要。本综述概述了 IGF-1R 信号在实体瘤中的作用，特别是在 NSCLC 中的作用，并提供了临床数据概述。
