{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:57:32Z","timestamp":1776185852050,"version":"3.50.1"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,12,10]],"date-time":"2016-12-10T00:00:00Z","timestamp":1481328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM101430"],"award-info":[{"award-number":["R01 GM101430"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS-1407548"],"award-info":[{"award-number":["DMS-1407548"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1-EB001988-15"],"award-info":[{"award-number":["RO1-EB001988-15"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Objective: Using electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.<\/jats:p><jats:p>Method: We applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.<\/jats:p><jats:p>Results: From EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.<\/jats:p><jats:p>Conclusions: This is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing.<\/jats:p>","DOI":"10.1093\/jamia\/ocw161","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T20:07:04Z","timestamp":1478635624000},"page":"565-576","source":"Crossref","is-referenced-by-count":13,"title":["Synergistic drug combinations from electronic health records and gene expression"],"prefix":"10.1093","volume":"24","author":[{"given":"Yen S","family":"Low","sequence":"first","affiliation":[{"name":"Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USA"}]},{"given":"Aaron C","family":"Daugherty","sequence":"additional","affiliation":[{"name":"twoXAR, Inc., Palo Alto, CA, USA"}]},{"given":"Elizabeth A","family":"Schroeder","sequence":"additional","affiliation":[{"name":"twoXAR, Inc., Palo Alto, CA, USA"}]},{"given":"William","family":"Chen","sequence":"additional","affiliation":[{"name":"Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USA"}]},{"given":"Tina","family":"Seto","sequence":"additional","affiliation":[{"name":"Clinical Informatics, Stanford University"}]},{"given":"Susan","family":"Weber","sequence":"additional","affiliation":[{"name":"Clinical Informatics, Stanford University"}]},{"given":"Michael","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Statistics, Stanford University"}]},{"given":"Trevor","family":"Hastie","sequence":"additional","affiliation":[{"name":"Department of Statistics, Stanford University"},{"name":"Department of Health Research and Policy, Stanford University"}]},{"given":"Maya","family":"Mathur","sequence":"additional","affiliation":[{"name":"Quantitative Sciences Unit, Stanford University"}]},{"given":"Manisha","family":"Desai","sequence":"additional","affiliation":[{"name":"Quantitative Sciences Unit, Stanford University"}]},{"given":"Carl","family":"Farrington","sequence":"additional","affiliation":[{"name":"twoXAR, Inc., Palo Alto, CA, USA"}]},{"given":"Andrew A","family":"Radin","sequence":"additional","affiliation":[{"name":"twoXAR, Inc., Palo Alto, CA, USA"}]},{"given":"Marina","family":"Sirota","sequence":"additional","affiliation":[{"name":"twoXAR, Inc., Palo Alto, CA, USA"}]},{"given":"Pragati","family":"Kenkare","sequence":"additional","affiliation":[{"name":"Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA"}]},{"given":"Caroline A","family":"Thompson","sequence":"additional","affiliation":[{"name":"Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA"}]},{"given":"Peter P","family":"Yu","sequence":"additional","affiliation":[{"name":"Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA"}]},{"given":"Scarlett L","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Health Research and Policy, Stanford University"},{"name":"Cancer Prevention Institute of California, Fremont, CA, USA"}]},{"suffix":"Jr","given":"George W","family":"Sledge","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine, Stanford University"}]},{"given":"Allison W","family":"Kurian","sequence":"additional","affiliation":[{"name":"Department of Health Research and Policy, Stanford University"},{"name":"Division of Oncology, Department of Medicine, Stanford University"}]},{"given":"Nigam H","family":"Shah","sequence":"additional","affiliation":[{"name":"Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USA"}]}],"member":"286","published-online":{"date-parts":[[2016,12,26]]},"reference":[{"key":"2020110612435524400_ocw161-B1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1136\/amiajnl-2014-002649","article-title":"Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality","volume":"22","author":"Xu","year":"2015","journal-title":"J. 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Clin."},{"key":"2020110612435524400_ocw161-B41","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1023\/A:1011240019516","article-title":"Socioeconomic status and breast cancer incidence in California for different race\/ethnic groups","volume":"12","author":"Yost","year":"2001","journal-title":"Cancer Causes Control."},{"key":"2020110612435524400_ocw161-B42","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2147\/BCTT.S12955","article-title":"Antiemetic therapy options for chemotherapy-induced nausea and vomiting in breast cancer patients","volume":"2011","author":"Yeo","year":"2011","journal-title":"Breast Cancer Targets Ther."},{"key":"2020110612435524400_ocw161-B43","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/ijc.23718","article-title":"Combination regimen with statins and NSAIDs: A promising strategy for cancer chemoprevention","volume":"123","author":"Xiao","year":"2008","journal-title":"Int. J. Cancer."},{"key":"2020110612435524400_ocw161-B44","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.cgh.2012.08.037","article-title":"Statins and colorectal cancer","volume":"11","author":"Lochhead","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"2020110612435524400_ocw161-B45","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1002\/ijc.22796","article-title":"Individual and joint use of statins and low-dose aspirin and risk of colorectal cancer: a population-based case-control study","volume":"121","author":"Hoffmeister","year":"2007","journal-title":"Int. J. Cancer."},{"key":"2020110612435524400_ocw161-B46","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.metabol.2013.10.005","article-title":"Statins: protectors or pretenders in prostate cancer? 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Oncol."},{"key":"2020110612435524400_ocw161-B49","doi-asserted-by":"crossref","first-page":"7455","DOI":"10.1038\/sj.onc.1209085","article-title":"Perturbations of the AKT signaling pathway in human cancer","volume":"24","author":"Altomare","year":"2005","journal-title":"Oncogene."},{"key":"2020110612435524400_ocw161-B50","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1074\/jbc.M115.702571","article-title":"AP-1 is a key regulator of proinflammatory cytokine TNF\u03b1-mediated triple-negative breast cancer progression","volume":"291","author":"Qiao","year":"2016","journal-title":"J.\u00a0Biol. Chem."},{"key":"2020110612435524400_ocw161-B51","doi-asserted-by":"crossref","first-page":"6004","DOI":"10.1038\/onc.2010.336","article-title":"Regulation of C\/EBPbeta1 by Ras in mammary epithelial cells and the role of C\/EBPbeta1 in oncogene-induced senescence","volume":"29","author":"Atwood","year":"2010","journal-title":"Oncogene."},{"key":"2020110612435524400_ocw161-B52","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.bcp.2006.10.026","article-title":"Inducible overexpression of c-Jun in MCF7 cells causes resistance to vinblastine via inhibition of drug-induced apoptosis and senescence at a step subsequent to mitotic arrest","volume":"73","author":"Duan","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"2020110612435524400_ocw161-B53","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1002\/jcp.24019","article-title":"Nuclear IRS-1 and cancer","volume":"227","author":"Reiss","year":"2012","journal-title":"J. Cell Physiol."},{"key":"2020110612435524400_ocw161-B54","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.canlet.2013.03.030","article-title":"IRS1 is highly expressed in localized breast tumors and regulates the sensitivity of breast cancer cells to chemotherapy, while IRS2 is highly expressed in invasive breast tumors","volume":"338","author":"Porter","year":"2013","journal-title":"Cancer Lett."},{"key":"2020110612435524400_ocw161-B55","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s10549-009-0632-6","article-title":"Nuclear IRS-1 predicts tamoxifen response in patients with early breast cancer","volume":"123","author":"Migliaccio","year":"2010","journal-title":"Breast Cancer Res. Treat."},{"key":"2020110612435524400_ocw161-B56","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1158\/1541-7786.MCR-15-0423","article-title":"Blockade of AP-1 potentiates endocrine therapy and overcomes resistance","volume":"14","author":"Malorni","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"2020110612435524400_ocw161-B57","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s10549-008-0228-6","article-title":"Association between NSAIDs use and breast cancer risk: a systematic review and meta-analysis","volume":"117","author":"Zhao","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"2020110612435524400_ocw161-B58","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1053\/j.seminoncol.2004.03.042","article-title":"The role of COX-2 inhibition in breast cancer treatment and prevention","volume":"31","author":"Arun","year":"2004","journal-title":"Semin. Oncol."},{"key":"2020110612435524400_ocw161-B59","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/annonc\/mdn693","article-title":"Role of combination therapy with aromatase and cyclooxygenase-2 inhibitors in patients with metastatic breast cancer","volume":"20","author":"Falandry","year":"2009","journal-title":"Ann. Oncol."},{"key":"2020110612435524400_ocw161-B60","doi-asserted-by":"crossref","first-page":"19065","DOI":"10.1073\/pnas.1318247110","article-title":"Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention","volume":"110","author":"Liu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. 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