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

作者：Jouhyun Jeon, Satra Nim, Joan Teyra, Alessandro Datti, Jeffrey L. Wrana, Sachdev S. Sidhu, Jason Moffat, Philip M. Kim · 发表于：Genome Medicine · 年份：2014 · DOI：10.1186/s13073-014-0057-7 · 被引用次数：167 · 研究领域：Computational Drug Discovery Methods、vaccines and immunoinformatics approaches、Monoclonal and Polyclonal Antibodies Research

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.