Cargando…

Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy

With multiple omics strategies being applied to several cancer genomics projects, researchers have the opportunity to develop a rational planning of targeted cancer therapy. The investigation of such numerous and diverse pharmacogenomic datasets is a complex task. It requires biological knowledge an...

Descripción completa

Detalles Bibliográficos
Autores principales: Belizário, José E., Sangiuliano, Beatriz A., Perez-Sosa, Marcela, Neyra, Jennifer M., Moreira, Dayson F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040751/
https://www.ncbi.nlm.nih.gov/pubmed/27746730
http://dx.doi.org/10.3389/fphar.2016.00312
_version_ 1782456277802156032
author Belizário, José E.
Sangiuliano, Beatriz A.
Perez-Sosa, Marcela
Neyra, Jennifer M.
Moreira, Dayson F.
author_facet Belizário, José E.
Sangiuliano, Beatriz A.
Perez-Sosa, Marcela
Neyra, Jennifer M.
Moreira, Dayson F.
author_sort Belizário, José E.
collection PubMed
description With multiple omics strategies being applied to several cancer genomics projects, researchers have the opportunity to develop a rational planning of targeted cancer therapy. The investigation of such numerous and diverse pharmacogenomic datasets is a complex task. It requires biological knowledge and skills on a set of tools to accurately predict signaling network and clinical outcomes. Herein, we describe Web-based in silico approaches user friendly for exploring integrative studies on cancer biology and pharmacogenomics. We briefly explain how to submit a query to cancer genome databases to predict which genes are significantly altered across several types of cancers using CBioPortal. Moreover, we describe how to identify clinically available drugs and potential small molecules for gene targeting using CellMiner. We also show how to generate a gene signature and compare gene expression profiles to investigate the complex biology behind drug response using Connectivity Map. Furthermore, we discuss on-going challenges, limitations and new directions to integrate molecular, biological and epidemiological information from oncogenomics platforms to create hypothesis-driven projects. Finally, we discuss the use of Patient-Derived Xenografts models (PDXs) for drug profiling in vivo assay. These platforms and approaches are a rational way to predict patient-targeted therapy response and to develop clinically relevant small molecules drugs.
format Online
Article
Text
id pubmed-5040751
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-50407512016-10-14 Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy Belizário, José E. Sangiuliano, Beatriz A. Perez-Sosa, Marcela Neyra, Jennifer M. Moreira, Dayson F. Front Pharmacol Pharmacology With multiple omics strategies being applied to several cancer genomics projects, researchers have the opportunity to develop a rational planning of targeted cancer therapy. The investigation of such numerous and diverse pharmacogenomic datasets is a complex task. It requires biological knowledge and skills on a set of tools to accurately predict signaling network and clinical outcomes. Herein, we describe Web-based in silico approaches user friendly for exploring integrative studies on cancer biology and pharmacogenomics. We briefly explain how to submit a query to cancer genome databases to predict which genes are significantly altered across several types of cancers using CBioPortal. Moreover, we describe how to identify clinically available drugs and potential small molecules for gene targeting using CellMiner. We also show how to generate a gene signature and compare gene expression profiles to investigate the complex biology behind drug response using Connectivity Map. Furthermore, we discuss on-going challenges, limitations and new directions to integrate molecular, biological and epidemiological information from oncogenomics platforms to create hypothesis-driven projects. Finally, we discuss the use of Patient-Derived Xenografts models (PDXs) for drug profiling in vivo assay. These platforms and approaches are a rational way to predict patient-targeted therapy response and to develop clinically relevant small molecules drugs. Frontiers Media S.A. 2016-09-29 /pmc/articles/PMC5040751/ /pubmed/27746730 http://dx.doi.org/10.3389/fphar.2016.00312 Text en Copyright © 2016 Belizário, Sangiuliano, Perez-Sosa, Neyra and Moreira. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Belizário, José E.
Sangiuliano, Beatriz A.
Perez-Sosa, Marcela
Neyra, Jennifer M.
Moreira, Dayson F.
Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy
title Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy
title_full Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy
title_fullStr Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy
title_full_unstemmed Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy
title_short Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy
title_sort using pharmacogenomic databases for discovering patient-target genes and small molecule candidates to cancer therapy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040751/
https://www.ncbi.nlm.nih.gov/pubmed/27746730
http://dx.doi.org/10.3389/fphar.2016.00312
work_keys_str_mv AT belizariojosee usingpharmacogenomicdatabasesfordiscoveringpatienttargetgenesandsmallmoleculecandidatestocancertherapy
AT sangiulianobeatriza usingpharmacogenomicdatabasesfordiscoveringpatienttargetgenesandsmallmoleculecandidatestocancertherapy
AT perezsosamarcela usingpharmacogenomicdatabasesfordiscoveringpatienttargetgenesandsmallmoleculecandidatestocancertherapy
AT neyrajenniferm usingpharmacogenomicdatabasesfordiscoveringpatienttargetgenesandsmallmoleculecandidatestocancertherapy
AT moreiradaysonf usingpharmacogenomicdatabasesfordiscoveringpatienttargetgenesandsmallmoleculecandidatestocancertherapy