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新兴基因组学和蛋白质组学技术在癌症药物靶点发现中的作用。

The role of emerging genomics and proteomics technologies in cancer drug target discovery.

作者信息

Onyango Patrick

机构信息

Department of Medicine, Johns Hopkins University School of Medicine, 1064 Ross, 720, Rutland Avenue, Baltimore, MD 21205, USA.

出版信息

Curr Cancer Drug Targets. 2004 Mar;4(2):111-24. doi: 10.2174/1568009043481588.

Abstract

Cancer drugs have traditionally been identified in screens designed to produce broad biological end points such as cell death. A serious undesired outcome of drugs discovered in these screens is that the mechanism of drug action is unknown and such drugs often have adverse side effects. Designing cancer drugs that act on specific targets offer the advantage that the mechanism of drug action can be understood and accurately monitored in clinical trials leading to development of better drugs. The pharmacological industry has recently shifted to a target directed drug discovery model. However, until recently potential cancer drug targets comprised of only a small fraction of the human genome. The human genome project and high-throughput structural and functional genomics have dramatically increased the number of cancer drug targets. Deciphering cancer drug targets requires the understanding of biochemical pathways that are affected in the cancer genome. It has been suggested that utilization of Single-nucleotide polymorphisms (SNPs) will aid in identifying individuals at high risk of developing certain cancers, and will also help in development of tailored medication or identify genetic profiles of specific drug action and toxicity. Achieving successful new cancer drug development schemes will require a merger of research disciplines that include pharmacology, genomics, comparative genomics, functional genomics, proteomics and bioinformatics. In this review the significance and challenges of these rapidly evolving technologies in cancer drug target discovery are discussed.

摘要

传统上,癌症药物是在旨在产生广泛生物学终点(如细胞死亡)的筛选中确定的。在这些筛选中发现的药物一个严重的不良后果是药物作用机制未知,而且这类药物往往有不良副作用。设计作用于特定靶点的癌症药物具有这样的优势:药物作用机制可以被理解,并且在临床试验中可以得到准确监测,从而开发出更好的药物。制药行业最近已转向靶向药物发现模式。然而,直到最近,潜在的癌症药物靶点仅占人类基因组的一小部分。人类基因组计划以及高通量结构和功能基因组学极大地增加了癌症药物靶点的数量。解读癌症药物靶点需要了解癌症基因组中受影响的生化途径。有人提出,利用单核苷酸多态性(SNP)将有助于识别患某些癌症风险高的个体,还将有助于开发定制药物或识别特定药物作用和毒性的基因图谱。要实现成功的新癌症药物开发方案,需要融合包括药理学、基因组学、比较基因组学、功能基因组学、蛋白质组学和生物信息学在内的研究学科。在这篇综述中,将讨论这些快速发展的技术在癌症药物靶点发现中的意义和挑战。

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