A systematic approach to identify novel cancer drug targets using machine learning, inhibitor design and high-throughput screening

被引:98
|
作者
Jeon, Jouhyun [1 ]
Nim, Satra [1 ]
Teyra, Joan [1 ]
Datti, Alessandro [4 ,5 ]
Wrana, Jeffrey L. [4 ]
Sidhu, Sachdev S. [1 ,2 ]
Moffat, Jason [1 ,2 ]
Kim, Philip M. [1 ,2 ,3 ]
机构
[1] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada
[2] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada
[3] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3E1, Canada
[4] Univ Toronto, Mt Sinai Hosp, Ctr Syst Biol, Samuel Lunenfeld Res Inst, Toronto, ON M5S 3E1, Canada
[5] Univ Perugia, Dept Agr Food & Environm Sci, I-06100 Perugia, Italy
来源
GENOME MEDICINE | 2014年 / 6卷
基金
加拿大自然科学与工程研究理事会; 新加坡国家研究基金会;
关键词
PEPTIDE RECOGNITION MODULES; HUMAN PANCREATIC CANCERS; MESSENGER-RNA EXPORT; GENE DELIVERY; SIGNALING PATHWAYS; SOMATIC MUTATION; LANDSCAPE; BREAST; RESOURCE; NETWORK;
D O I
10.1186/s13073-014-0057-7
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We present an integrated approach that predicts and validates novel anti-cancer drug targets. We first built a classifier that integrates a variety of genomic and systematic datasets to prioritize drug targets specific for breast, pancreatic and ovarian cancer. We then devised strategies to inhibit these anti-cancer drug targets and selected a set of targets that are amenable to inhibition by small molecules, antibodies and synthetic peptides. We validated the predicted drug targets by showing strong anti-proliferative effects of both synthetic peptide and small molecule inhibitors against our predicted targets.
引用
收藏
页数:18
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