title: Identifying differentially expressed genes and screening small molecule drugs for lapatinib-resistance of breast cancer by a bioinformatics strategy.
abstract: BACKGROUND
  Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method.
  
  
  METHODS
  We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance.
  
  
  RESULTS
  A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance.
  
  
  CONCLUSIONS
  The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.
authors.affiliation: Institute of Cancer, Xinqiao Hospital , Third Military Medical University, Chongqing, China E-mail : zhuowenlei@tmmu.edu.cn.
authors.forename: Wen-Lei
authors.initials: WL
authors.lastname: Zhuo
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Qi-Chao
authors.initials: QC
authors.lastname: Xie
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.forename: Zheng-Tang
authors.initials: ZT
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077341:Lapatinib; D011799:Quinazolines / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D054852:Small Molecule Libraries