Masonic Cancer Center, University of Minnesota420 Delaware Street SE, Minneapolis, MN, USA.
J Natl Cancer Inst. 2012 Jul 3;104(13):975-81. doi: 10.1093/jnci/djs258.
The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response, larger randomized phase III trials have not shown clear clinical benefit of targeting this pathway in combination with conventional strategies. These disappointing results have resulted in the discontinuation of several anti-IGF1R programs. However, the conduct of these trials has brought to the forefront several important factors that need to be considered in the conduct of future clinical trials. The need to develop biomarkers, a clearer understanding of insulin receptor function, and defining rational combination regimens all require further consideration. In this commentary, the current state of IGF1R inhibitors in cancer therapy is reviewed.
癌症靶向治疗的成功是毋庸置疑的；强有力的临床前证据已促使几种新的癌症治疗药物获得批准。I 型胰岛素样生长因子受体 (IGF1R) 似乎是这些有前途的新靶点之一。大量的人群和临床前数据都表明该途径是肿瘤细胞生物学的重要调节剂。尽管针对 IGF1R 的临床试验的早期结果显示出一些有反应的迹象，但更大规模的随机 III 期试验并未显示出针对该途径联合常规策略的明确临床获益。这些令人失望的结果导致了几种抗 IGF1R 方案的终止。然而，这些试验的开展突显了在未来临床试验中需要考虑的几个重要因素。需要开发生物标志物、更清楚地了解胰岛素受体的功能以及确定合理的联合治疗方案都需要进一步考虑。在这篇评论中，回顾了癌症治疗中 IGF1R 抑制剂的现状。
