Jang Su-Kyeong, Yoon Byung-Ha, Kang Seung Min, Yoon Yeo-Gha, Kim Seon-Young, Kim Wankyu
Ewha Research Center for Systems Biology, Department of Life Science, Division of Molecular & Life Sciences, Ewha Womans University, Seoul 03760, Korea.
Gene Editing Research Center, KRIBB, Daejeon 34141, Korea.
Mol Cells. 2019 Mar 31;42(3):237-244. doi: 10.14348/molcells.2018.0413. Epub 2019 Feb 12.
Understanding the mechanisms of cancer drug resistance is a critical challenge in cancer therapy. For many cancer drugs, various resistance mechanisms have been identified such as target alteration, alternative signaling pathways, epithelial-mesenchymal transition, and epigenetic modulation. Resistance may arise via multiple mechanisms even for a single drug, making it necessary to investigate multiple independent models for comprehensive understanding and therapeutic application. In particular, we hypothesize that different resistance processes result in distinct gene expression changes. Here, we present a web-based database, CDRgator (Cancer Drug Resistance navigator) for comparative analysis of gene expression signatures of cancer drug resistance. Resistance signatures were extracted from two different types of datasets. First, resistance signatures were extracted from transcriptomic profiles of cancer cells or patient samples and their resistance-induced counterparts for >30 cancer drugs. Second, drug resistance group signatures were also extracted from two large-scale drug sensitivity datasets representing ~1,000 cancer cell lines. All the datasets are available for download, and are conveniently accessible based on drug class and cancer type, along with analytic features such as clustering analysis, multidimensional scaling, and pathway analysis. CDRgator allows meta-analysis of independent resistance models for more comprehensive understanding of drug-resistance mechanisms that is difficult to accomplish with individual datasets alone (database URL: http://cdrgator.ewha.ac.kr).
了解癌症耐药机制是癌症治疗中的一项关键挑战。对于许多癌症药物，已确定了多种耐药机制，如靶点改变、替代信号通路、上皮-间质转化和表观遗传调控。即使对于单一药物，耐药也可能通过多种机制产生，因此有必要研究多个独立模型以进行全面理解和治疗应用。特别是，我们假设不同的耐药过程会导致不同的基因表达变化。在此，我们展示了一个基于网络的数据库CDRgator（癌症耐药导航器），用于癌症耐药基因表达特征的比较分析。耐药特征是从两种不同类型的数据集中提取的。首先，从癌细胞或患者样本及其耐药诱导对应物的转录组谱中提取了超过30种癌症药物的耐药特征。其次，还从代表约1000个癌细胞系的两个大规模药物敏感性数据集中提取了耐药组特征。所有数据集均可下载，并可根据药物类别和癌症类型方便地访问，同时还具备聚类分析、多维标度和通路分析等分析功能。CDRgator允许对独立的耐药模型进行荟萃分析，以便更全面地了解耐药机制，而这仅靠单个数据集是难以实现的（数据库网址：http://cdrgator.ewha.ac.kr）。
