Drug Development Unit, Royal Marsden NHS Foundation Trust, Section of Medicine, The Institute of Cancer Research, Sutton, Surrey, SM2 5PT, UK.
Expert Opin Investig Drugs. 2011 Sep;20(9):1293-304. doi: 10.1517/13543784.2011.602630. Epub 2011 Jul 22.
There are clear preclinical data that support the involvement of the insulin-like growth factor (IGF) signaling pathway in oncogenesis and cancer progression. Such evidence has led to the design and conduct of drug development programs targeting the IGF-I receptor (IGF-IR) over the past 10 years.
This review details the structure and function of different members of the IGF system and related pathways, describes the rationale for targeting IGF-IR in cancer and updates the current advances in drug development. The preclinical development of figitumumab, the furthest developed mAb against IGF-IR, is examined as well as the reported data from Phase I - III clinical trials. Future prospects for this target and pathway are also discussed.
While there have been both successes and failures in the development of novel targeted therapeutics targeting the IGF pathway, the evaluation of such agents should continue, with greater emphasis placed on combinatorial strategies and the development of predictive biomarkers that enhance antitumor responses through appropriate patient selection.
有明确的临床前数据表明胰岛素样生长因子(IGF)信号通路参与了肿瘤的发生和发展。这些证据促使人们在过去 10 年中设计并开展了针对 IGF-1 受体(IGF-IR)的药物开发项目。
本综述详细描述了 IGF 系统及其相关途径的不同成员的结构和功能,描述了针对 IGF-IR 进行癌症治疗的原理,并更新了药物开发的最新进展。还研究了针对 IGF-IR 开发的最先进的单克隆抗体 figitumumab 的临床前开发情况以及 I 期至 III 期临床试验的报告数据。还讨论了该靶点和途径的未来前景。
虽然针对 IGF 通路的新型靶向治疗药物的开发既有成功也有失败,但仍应继续评估这些药物,更加强调联合策略和开发预测性生物标志物,通过适当的患者选择来增强抗肿瘤反应。