Targeting the PI3K-AKT-mTOR signaling network in cancer

作     者：Khurum H. Khan Timothy A. Yap Li Yan David Cunningham 

作者机构：GI and Lymphoma Unit The Royal Marsden NHS Foundation Trust Drug Development Unit The Royal Marsden NHS Foundation Trust Merck & Co. Inc. US Chinese Anti-Cancer Association School of Oncology Peking University Cancer Hospital Beijing Cancer Hospital 

出 版 物：《Chinese Journal of Cancer》 (Chin. J. Cancer)

年 卷 期：2013年第32卷第5期

页      面：253-265页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：The Drug Development Unit of the Royal Marsden NHS Foundation Trust The Institute of Cancer Research is supported in part by a program grant from Cancer Research U.K Support was also provided by the Experimental Cancer Medicine Centre (to The Institute of Cancer Research) the National Institute for Health Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research) 

主　　题：信号网络 癌症 靶向治疗 生物标志物 磷酸肌醇 细胞生长 雷帕霉素 哺乳动物 

摘      要：The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted therapies against mTOR, a vital substrate along this pathway, led to the approval of allosteric inhibitors, including everolimus and temsirolimus, for the treatment of breast, renal, and pancreatic cancers. However, the suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel therapies against critical nodes of this pathway are therefore being actively investigated in the clinic in multiple tumour types. In this review, we focus on the progress of these agents in clinical development along with their biological rationale, the need of predictive biomarkers and various combination strategies, which will be useful in counteracting the mechanisms of resistance to this class of drugs.