Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Center for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China.
Nucleic Acids Res. 2017 Jul 3;45(W1):W215-W221. doi: 10.1093/nar/gkx400.
Cancer therapies have experienced rapid progress in recent years, with a number of novel small-molecule kinase inhibitors and monoclonal antibodies now being widely used to treat various types of human cancers. During cancer treatments, mutations can have important effects on drug sensitivity. However, the relationship between tumor genomic profiles and the effectiveness of cancer drugs remains elusive. We introduce Mutation To Cancer Therapy Scan (mTCTScan) web server (http://jjwanglab.org/mTCTScan) that can systematically analyze mutations affecting cancer drug sensitivity based on individual genomic profiles. The platform was developed by leveraging the latest knowledge on mutation-cancer drug sensitivity associations and the results from large-scale chemical screening using human cancer cell lines. Using an evidence-based scoring scheme based on current integrative evidences, mTCTScan is able to prioritize mutations according to their associations with cancer drugs and preclinical compounds. It can also show related drugs/compounds with sensitivity classification by considering the context of the entire genomic profile. In addition, mTCTScan incorporates comprehensive filtering functions and cancer-related annotations to better interpret mutation effects and their association with cancer drugs. This platform will greatly benefit both researchers and clinicians for interrogating mechanisms of mutation-dependent drug response, which will have a significant impact on cancer precision medicine.
近年来,癌症疗法取得了快速进展,许多新型小分子激酶抑制剂和单克隆抗体现已广泛用于治疗各种人类癌症。在癌症治疗过程中,突变会对药物敏感性产生重要影响。然而,肿瘤基因组图谱与癌症药物疗效之间的关系仍然难以捉摸。我们引入了 Mutation To Cancer Therapy Scan (mTCTScan) 网络服务器(http://jjwanglab.org/mTCTScan),该服务器可以根据个体基因组图谱系统地分析影响癌症药物敏感性的突变。该平台是利用最新的突变与癌症药物敏感性关联知识以及使用人类癌细胞系进行大规模化学筛选的结果开发的。mTCTScan 采用基于当前综合证据的循证评分方案,根据与癌症药物和临床前化合物的关联对突变进行优先级排序。它还可以通过考虑整个基因组图谱的上下文,根据敏感性分类显示相关药物/化合物。此外,mTCTScan 还整合了全面的过滤功能和癌症相关注释,以更好地解释突变的影响及其与癌症药物的关联。该平台将极大地造福于研究人员和临床医生,有助于探究突变依赖性药物反应的机制,这将对癌症精准医学产生重大影响。