Catálogo de Investigaciones 2015-2016

152 FACULTAD Pharmacogenomics and cancer: study of the sensitivity and resistance to drugs derived from the analysis of genomic data in cancer Differences based on genome and gene expression affect the pharmacokinetics and pharmacodynamics of a drug in the body. Pharmacogenomics allows the search for and proposal of “target genes” and can facilitate the identification of biomarkers of the different diseases and disease states. Search strategies for “target genes” may rely on the analysis of overall expression and gene activity profiles obtained in response to a drug and association or correlation studies derived from those responses. The primary goal of the research is to find new drug-gene relationships that indicate possible interactions in which a particular drug or compound acts on a particular cancer gene target. When a relationship is found and it is “significant and positive,” it is possible to identify genes with “sensitivity” to certain drugs. When a relationship is found and it is “significant and negative”, it is possible to identify genes that confer “resistance” to certain drugs. All these results are derived from analysis based on three main variables: drug, gene and cell line. To this end, a comprehensive list of over 800 cancer related genes, including oncogenes, tumor suppressor genes and genes with dual activity or whose mode of operation has yet to be determined, was compiled. In addition, we compiled a list of genes involved in drug resistance (particularly in cancer drug resistance) and determined their Pearson and Spearman correlation to FDA approved onco-drugs. We performed robust correlation analyses (with their respective p-value calculations) between the genes and drugs of interest. The results shed light to compounds that are promising drug candidates, with better correlations than with the most current drugs to inhibit several oncogenes. These predictions open the way to finding more effective new drugs and developing alternative therapies. dra. monica m. arroyo colegio de ciencias - pucpr oscar gutiérrez usal pharmacy student dr. javier de las rivas collaborator and cic-ibmcc group leader cancer pharmacogenomics drug repositioning bioinformatics