在藥物的研制過程中，有很多意外之喜。例如，萬艾可（偉哥）最初用于治療心臟疾病,，后來卻發(fā)現(xiàn)它對勃起功能障礙和肺動脈高壓效果不錯。而現(xiàn)在,，科學(xué)家又發(fā)現(xiàn),，潰瘍藥可以治療肺癌。
8月17日,，《科學(xué)—轉(zhuǎn)化醫(yī)學(xué)》雜志在線發(fā)布的一項最新研究顯示，潰瘍藥西咪替丁能抑制肺癌的腫瘤細(xì)胞生長,。美國斯坦福大學(xué)醫(yī)學(xué)院的研究者利用計算機(jī)把藥物與治療作用進(jìn)行交叉配對后發(fā)現(xiàn),，西咪替丁對30%—40%肺癌具有治療作用。另外,，抗癲癇藥托吡酯能明顯緩解克羅恩氏病引起的腹瀉,。(生物谷 Bioon.com)
doi:10.1126/scitranslmed.3001318
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Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data
Sirota, Marina; Dudley, Joel T.; Kim, Jeewon; Chiang, Annie P.; Morgan, Alex A.; Sweet-Cordero, Alejandro; Sage, Julien; Butte, Atul J.
The application of established drug compounds to new therapeutic indications, known as drug repositioning, offers severaladvantages over traditional drug development, including reduced development costs and shorter paths to approval. Recent approachesto drug repositioning use high-throughput experimental approaches to assess a compound’s potential therapeutic qualities.Here, we present a systematic computational approach to predict novel therapeutic indications on the basis of comprehensivetesting of molecular signatures in drug-disease pairs. We integrated gene expression measurements from 100 diseases and geneexpression measurements on 164 drug compounds, yielding predicted therapeutic potentials for these drugs. We recovered manyknown drug and disease relationships using computationally derived therapeutic potentials and also predict many new indicationsfor these 164 drugs. We experimentally validated a prediction for the antiulcer drug cimetidine as a candidate therapeuticin the treatment of lung adenocarcinoma, and demonstrate its efficacy both in vitro and in vivo using mouse xenograft models.This computational method provides a systematic approach for repositioning established drugs to treat a wide range of humandiseases.
