Casa Angelo J, Dearth Robert K, Litzenburger Beate C, Lee Adrian V, Cui Xiaojiang
Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Front Biosci. 2008 May 1;13:3273-87. doi: 10.2741/2925.
The insulin-like growth factor (IGF) ligands stimulate cellular proliferation and survival by activating the type I insulin-like growth factor receptor (IGF-IR). As a result, the IGF signaling system is implicated in a number of cancers, including those of the breast, prostate, and lung. In addition to mitogenic and anti-apoptotic roles that may directly influence tumor development, IGF-IR also appears to be a critical determinant of response to numerous cancer therapies. This review describes the role of the IGF-IR pathway in mediating resistance to both general cytotoxic therapies, such as radiation and chemotherapy, and targeted therapies, such as tamoxifen and trastuzumab. It concludes with a description of approaches to target IGF-IR and argues that inhibition of IGF signaling, in conjunction with standard therapies, may enhance the response of cancer cells to multiple modalities.
胰岛素样生长因子（IGF）配体通过激活I型胰岛素样生长因子受体（IGF-IR）刺激细胞增殖和存活。因此，IGF信号系统与多种癌症有关，包括乳腺癌、前列腺癌和肺癌。除了可能直接影响肿瘤发展的促有丝分裂和抗凋亡作用外，IGF-IR似乎也是对多种癌症治疗反应的关键决定因素。本综述描述了IGF-IR途径在介导对一般细胞毒性疗法（如放疗和化疗）以及靶向疗法（如他莫昔芬和曲妥珠单抗）耐药中的作用。最后描述了靶向IGF-IR的方法，并认为抑制IGF信号与标准疗法相结合可能增强癌细胞对多种治疗方式的反应。
