title: Identifying kinase dependency in cancer cells by integrating high-throughput drug screening and kinase inhibition data.
abstract: BACKGROUND
  Targeted kinase inhibitors have dramatically improved cancer treatment, but kinase dependency for an individual patient or cancer cell can be challenging to predict. Kinase dependency does not always correspond with gene expression and mutation status. High-throughput drug screens are powerful tools for determining kinase dependency, but drug polypharmacology can make results difficult to interpret.
  
  
  RESULTS
  We developed Kinase Addiction Ranker (KAR), an algorithm that integrates high-throughput drug screening data, comprehensive kinase inhibition data and gene expression profiles to identify kinase dependency in cancer cells. We applied KAR to predict kinase dependency of 21 lung cancer cell lines and 151 leukemia patient samples using published datasets. We experimentally validated KAR predictions of FGFR and MTOR dependence in lung cancer cell line H1581, showing synergistic reduction in proliferation after combining ponatinib and AZD8055.
  
  
  METHODS
  KAR can be downloaded as a Python function or a MATLAB script along with example inputs and outputs at: http://tanlab.ucdenver.edu/KAR/.
  
  
  BACKGROUND
  aikchoon.tan@ucdenver.edu.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, Department of Medicine.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Ryall
authors.affiliation: Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, Department of Medicine.
authors.forename: Jimin
authors.initials: J
authors.lastname: Shin
authors.affiliation: Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, Department of Medicine.
authors.forename: Minjae
authors.initials: M
authors.lastname: Yoo
authors.affiliation: Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Trista K
authors.initials: TK
authors.lastname: Hinz
authors.affiliation: Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, Department of Medicine.
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Computer Science and Engineering, Korea University, Seoul, Korea and.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Kang
authors.affiliation: Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, Department of Medicine.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Heasley
authors.affiliation: Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, Department of Medicine, Department of Computer Science and Engineering, Korea University, Seoul, Korea and Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Aik Choon
authors.initials: AC
authors.lastname: Tan
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004357:Drug Synergism; D020869:Gene Expression Profiling; D057166:High-Throughput Screening Assays; D006801:Humans; D015151:Immunoblotting; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D058570:TOR Serine-Threonine Kinases