在药物的研制过程中，有很多意外之喜。例如，万艾可（伟哥）最初用于治疗心脏疾病，后来却发现它对勃起功能障碍和肺动脉高压效果不错。而现在，科学家又发现，溃疡药可以治疗肺癌。
8月17日，《科学—转化医学》杂志在线发布的一项最新研究显示，溃疡药西咪替丁能抑制肺癌的肿瘤细胞生长。美国斯坦福大学医学院的研究者利用计算机把药物与治疗作用进行交叉配对后发现，西咪替丁对30%—40%肺癌具有治疗作用。另外，抗癫痫药托吡酯能明显缓解克罗恩氏病引起的腹泻。(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.
