Allosteric therapies for lung cancer

被引:8
作者
Ling, Ye [1 ]
Jing, Meiling [1 ]
Wang, Xiang-dong [1 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Biomed Res Ctr, Ctr Clin Bioinformat,Shanghai Inst Clin Bioinform, Shanghai 200433, Peoples R China
关键词
Allostery; Allosteric drug; Lung cancer; Epidermal growth factor receptor; Signal transduction pathway; GROWTH-FACTOR-RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; TYROSINE KINASE INHIBITORS; PROTEIN-COUPLED RECEPTORS; ADVANCED SOLID TUMORS; IN-VIVO VALIDATION; PHASE-II; DRUG DISCOVERY; MEK INHIBITOR; EGF RECEPTOR;
D O I
10.1007/s10555-015-9567-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Allostery is a regulation at a distance by conveying information from one site to another and an intrinsic property of dynamic proteins. Allostery plays an essential role in receptor trafficking, signal transmission, controlled catalysis, gene turn on/off, or cell apoptosis. Allosteric mutations are considered as one of causes responsible for cancer development, leading to "allosteric diseases" by stabilizing an active or inactive conformation or changing the dynamic distribution of preexisting propagation pathways. The present article mainly focuses on the potential of allosteric therapies for lung cancer. Allosteric drugs may have several advantages over traditional drugs. The epidermal growth factor receptor mutations and signaling pathways downstream (such as PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways) were suggested to play a key role in lung cancer and considered as targets of allosteric therapy. Some allosteric inhibitors for lung cancer-specific targets and a series of preclinical trials of allosteric inhibitors for lung cancer have been developed and reported. We expect that allosteric therapies will gain more attentions to develop combinatorial strategies for lung cancer and metastasis.
引用
收藏
页码:303 / 312
页数:10
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