Masonic Cancer CenterUniversity of Minnesota, Minneapolis, Minnesota, USA
J Mol Endocrinol. 2018 Jul;61(1):T61-T68. doi: 10.1530/JME-17-0261. Epub 2018 Jan 29.
Early preclinical and population data suggested a role for the type I insulin-like growth factor receptor (IGF1R) in the regulation of breast cancer growth and survival. To target this pathway, multiple monoclonal antibodies and tyrosine kinase inhibitors were developed and tested in clinical trials. While some of the early clinical trials suggested a benefit for these drugs, none of the attempts showed improved outcomes when compared to conventional therapy. This failure of the IGF1R inhibitors was pronounced in breast cancer; multiple trials testing IGF1R inhibition in estrogen receptor-positive breast cancer were conducted, none showed benefit. This review will evaluate the rationale for IGF1R inhibition, discuss results of the clinical trials and suggest a path forward.
早期的临床前和人群数据表明，I 型胰岛素样生长因子受体 (IGF1R) 在调节乳腺癌的生长和存活方面发挥作用。为了靶向这条通路，多种单克隆抗体和酪氨酸激酶抑制剂被开发出来并在临床试验中进行了测试。虽然一些早期的临床试验表明这些药物有益，但与传统疗法相比，没有一种尝试显示出改善的结果。这种 IGF1R 抑制剂在乳腺癌中的失效非常明显；多项试验测试了 IGF1R 抑制剂在雌激素受体阳性乳腺癌中的作用，但均未显示获益。这篇综述将评估 IGF1R 抑制的原理，讨论临床试验的结果，并提出前进的方向。
