title: A sub-pathway based method to identify candidate drugs for glioblastomas.
abstract: Glioblastomas (GBM) are the most common primary malignant brain tumors with a high invasiveness and resistance to radiation and other treatments. The need for the development of new therapeutic agents for GBM is urgent. Here, we aimed to explore the metabolic mechanism of GBM and identified potential novel drugs for GBM by a sub-pathway-based method. By using the GBM microarray data from "The Cancer Genome Atlas" database, we first identified the 274 differentially expressed genes between GBM and normal samples. Then, we identified 18 significant enriched metabolic sub-pathways that may involve in the development of GBM. Finally, by an integrated analysis of GBM-involved sub-pathways and drug-affected sub-pathways, we identified 66 novel small-molecular drugs capable to target the GBM-involved sub-pathways. Our method could not only identify existing drug (paclitaxel) for GBM, but also predict potentially novel agents (pergolide) that might have therapeutic effects. We also experimentally verified that pergolide could induce GBM cell death. These candidate small-molecular drugs identified by our approach may provide insights into a novel therapy approach for GBM.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Bao Jian Road 148, Harbin, 150081, People's Republic of China.
authors.forename: Yong-ri
authors.initials: YR
authors.lastname: Zheng
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.forename: Jian-jiao
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019295:Computational Biology; D030562:Databases, Protein; D055808:Drug Discovery / Q000379:methods*; D005909:Glioblastoma / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D010479:Pergolide / Q000494:pharmacology; D046888:Tissue Array Analysis
chemical_list: D000970:Antineoplastic Agents; D010479:Pergolide