文献类型：期刊文献

英文题名：Insulin-like Growth Factor-1 Receptor (IGF-1R) Kinase Inhibitors in Cancer Therapy: Advances and Perspectives

作者：Xue, Mengzhu[1];Cao, Xianwen[1];Zhong, Ye[1];Kuang, Dong[1];Liu, Xiaofeng[1];Zhao, Zhenjiang[1];Li, Honglin[1]

机构：[1]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China

年份：2012

卷号：18

期号：20

起止页码：2901

外文期刊名：CURRENT PHARMACEUTICAL DESIGN

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000306547500007)】；

基金：This work was supported by the Shanghai Committee of Science and Technology (grants 10431902600, 11DZ2260600 and 09DZ1975700), the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (grants 21173076 and 81102375), the Special Fund for Major State Basic Research Project (grants 2009CB918501 and 2011CB910200), and the National S&T Major Project of China (grant 2011ZX09307-002-03). Honglin Li is also sponsored by Shanghai Rising-Star Program (grant 10QA1401800) and Program for New Century Excellent Talents in University (grant NCET-100378).

语种：英文

外文关键词：Receptor tyrosine kinase; IGF-1R; IR; EGFR; small molecule inhibitors; anticancer strategies; signaling transduction pathway; network pharmacology

摘要：The insulin-like growth factors (IGF) and their receptors play pivotal roles in cellular signaling transduction and thus regulate cell growth, differentiation, apoptosis, transformation and other important physiological progresses. The insulin-like growth factor 1 receptor (IGF-1R) mainly engages in the Ras/mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, and also forms cross-talk with the epidermal growth factor receptor (EGFR) pathway. Currently, it draws more attention since its overexpression has been demonstrated in various human cancers, such as colorectal cancer, breast cancer, prostate cancer and lung tumors, thus the strategy targeting the IGF-1R would be promising in treatment of these cancers. There are already dozens of agents developed for the inhibition of IGF-1R, which are categorized into monoclonal antibodies, small molecule inhibitors and so on. While in this review, small molecule inhibitors would be the focus for detailed discussion. Herein, we updated previously reported research papers and reviews in this field and summarized developments of small molecule inhibitors up to 2011. Finally, we proposed the application of network pharmacology methods to reconsider the clinical use of inhibitors with concomitant IR inhibition or other kinases inhibition, hoping that more optimal combinations would be obtained for cancer therapy.