Discovery of noncancer drug effects on survival in electronic health records of patients with cancer: A new paradigm for drug repurposing

Yonghui Wu, Jeremy L. Warner, Liwei Wang, Min Jiang, Jun Xu, Qingxia Chen, Hui Nian, Qi Dai, Xianglin Du, Ping Yang, Joshua C. Denny, Hongfang Liu, Hua Xu

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

PURPOSE Drug development is becoming increasingly expensive and time consuming. Drug repurposing is one potential solution to accelerate drug discovery. However, limited research exists on the use of electronic health record (EHR) data for drug repurposing, and most published studies have been conducted in a hypothesis-driven manner that requires a predefined hypothesis about drugs and new indications. Whether EHRs can be used to detect drug repurposing signals is not clear. We want to demonstrate the feasibility of mining large, longitudinal EHRs for drug repurposing by detecting candidate noncancer drugs that can potentially be used for the treatment of cancer. PATIENTS AND METHODS By linking cancer registry data to EHRs, we identified 43,310 patients with cancer treated at Vanderbilt University Medical Center (VUMC) and 98,366 treated at the Mayo Clinic. We assessed the effect of 146 noncancer drugs on cancer survival using VUMC EHR data and sought to replicate significant associations (false discovery rate, .1) using the identical approach with Mayo Clinic EHR data. To evaluate replicated signals further, we reviewed the biomedical literature and clinical trials on cancers for corroborating evidence. RESULTS We identified 22 drugs from six drug classes (statins, proton pump inhibitors, angiotensin-converting enzyme inhibitors, β-blockers, nonsteroidal anti-inflammatory drugs, and α-1 blockers) associated with improved overall cancer survival (false discovery rate, .1) from VUMC; nine of the 22 drug associations were replicated at the Mayo Clinic. Literature and cancer clinical trial evaluations also showed very strong evidence to support the repurposing signals from EHRs. CONCLUSION Mining of EHRs for drug exposure–mediated survival signals is feasible and identifies potential candidates for antineoplastic repurposing. This study sets up a new model of mining EHRs for drug repurposing signals.

Original languageEnglish (US)
JournalJCO Clinical Cancer Informatics
Volume3
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Health Informatics

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