Belizário José E, Sangiuliano Beatriz A, Perez-Sosa Marcela, Neyra Jennifer M, Moreira Dayson F
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo São Paulo, Brazil.
Front Pharmacol. 2016 Sep 29;7:312. doi: 10.3389/fphar.2016.00312. eCollection 2016.
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 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 assay. These platforms and approaches are a rational way to predict patient-targeted therapy response and to develop clinically relevant small molecules drugs.
随着多种组学策略应用于多个癌症基因组学项目,研究人员有机会制定合理的靶向癌症治疗计划。对如此众多且多样的药物基因组学数据集进行研究是一项复杂的任务。它需要生物学知识以及一套工具的使用技能,以便准确预测信号网络和临床结果。在此,我们描述了基于网络的、便于用户探索癌症生物学和药物基因组学综合研究的方法。我们简要解释了如何向癌症基因组数据库提交查询,以使用CBioPortal预测在几种癌症类型中哪些基因发生了显著改变。此外,我们描述了如何使用CellMiner识别临床上可用的药物以及用于基因靶向的潜在小分子。我们还展示了如何生成基因特征并比较基因表达谱,以使用连通性图谱研究药物反应背后的复杂生物学机制。此外,我们讨论了将肿瘤基因组学平台的分子、生物学和流行病学信息整合起来以创建假设驱动项目所面临的持续挑战、局限性和新方向。最后,我们讨论了使用患者来源的异种移植模型(PDXs)进行药物分析检测。这些平台和方法是预测患者靶向治疗反应以及开发临床相关小分子药物的合理途径。