Tao Yungan, Pinzi Valentina, Bourhis Jean, Deutsch Eric
Institute Gustave-Roussy and the Department of Radiation Oncology of Cancer Hospital, Fu Dan University, Shanghai, China.
Nat Clin Pract Oncol. 2007 Oct;4(10):591-602. doi: 10.1038/ncponc0934.
The insulin-like growth factor 1 (IGF1) signaling pathway is implicated in the development of cancer. High levels of circulating IGF1 and certain genetic polymorphisms of IGF1 and IGFBP3 are associated with an increased risk of several common cancers. The IGF1 receptor (IGF1R) has been shown to be expressed in a wide range of tumors, and IGF1R signaling is crucial for tumor transformation and the survival of malignant cells. Several monoclonal antibodies and small-molecule inhibitors have been tested in preclinical studies and early-phase clinical studies. IGF1R signaling interferes with numerous growth factors and receptors such as VEGF and EGFR. In the experimental system, IGF1R signaling has been found to correlate with resistance to therapies based on the inhibition of EGFR and HER2. This Review highlights the most relevant studies in this exciting area of research, focusing in particular on the role of IGF1R in resistance to other receptor-targeted therapies for cancer.
胰岛素样生长因子1（IGF1）信号通路与癌症的发生发展有关。循环中IGF1的高水平以及IGF1和IGFBP3的某些基因多态性与几种常见癌症的风险增加相关。已证明胰岛素样生长因子1受体（IGF1R）在多种肿瘤中表达，并且IGF1R信号传导对于肿瘤转化和恶性细胞的存活至关重要。几种单克隆抗体和小分子抑制剂已在临床前研究和早期临床研究中进行了测试。IGF1R信号传导会干扰多种生长因子和受体，如血管内皮生长因子（VEGF）和表皮生长因子受体（EGFR）。在实验系统中，已发现IGF1R信号传导与基于抑制EGFR和人表皮生长因子受体2（HER2）的治疗耐药性相关。本综述重点介绍了这一令人兴奋的研究领域中最相关的研究，尤其关注IGF1R在癌症其他受体靶向治疗耐药性中的作用。
