title: Prediction of Candidate Drugs for Treating Pancreatic Cancer by Using a Combined Approach.
abstract: Pancreatic cancer is the leading cause of death from solid malignancies worldwide. Currently, gemcitabine is the only drug approved for treating pancreatic cancer. Developing new therapeutic drugs for this disease is, therefore, an urgent need. The C-Map project has provided a wealth of gene expression data that can be mined for repositioning drugs, a promising approach to new drug discovery. Typically, a drug is considered potentially useful for treating a disease if the drug-induced differential gene expression profile is negatively correlated with the differentially expressed genes in the target disease. However, many of the potentially useful drugs (PUDs) identified by gene expression profile correlation are likely false positives because, in C-Map, the cultured cell lines to which the drug is applied are not derived from diseased tissues. To solve this problem, we developed a combined approach for predicting candidate drugs for treating pancreatic cancer. We first identified PUDs for pancreatic cancer by using C-Map-based gene expression correlation analyses. We then applied an algorithm (Met-express) to predict key pancreatic cancer (KPC) enzymes involved in pancreatic cancer metabolism. Finally, we selected candidates from the PUDs by requiring that their targets be KPC enzymes or the substrates/products of KPC enzymes. Using this combined approach, we predicted seven candidate drugs for treating pancreatic cancer, three of which are supported by literature evidence, and three were experimentally validated to be inhibitory to pancreatic cancer celllines.
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China.|Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China.|Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Biostatistics and Computational Biology, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Dong
authors.affiliation: Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China.|SHAANXI Kang Fu Hospital, Xi'an, Shaanxi province, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Biostatistics and Computational Biology, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*