基于肿瘤蛋白-蛋白相互作用网络的药物靶标发现（英文）

The OncoPPi network:cancer-associated protein-protein interaction networks for therapeutic target discovery

基因组学的快速发展在我们面前呈现出了一幅肿瘤基因组的总构架,但目前最大的挑战之一是怎样将这些大量基因组信息转化成针对癌症病人基因变化的有效治疗方法.针对这一挑战,美国国家癌症研究所建立了"癌症靶标研发(CTD2)联盟".作为国家联盟的一员,埃默里大学CTD2中心着重于对癌症基因功能的研究,建立蛋白-蛋白相互作用网络,以助发现新的癌症治疗靶点.为了实现这个目标,笔者团队通过高通量筛选技术和高通量信息学方法的共同应用,快速检测癌症相关蛋白的分子互相作用,并构建了与肿瘤相关的蛋白-蛋白相互作用网络(OncoPPi).此网络将癌症基因与相应的功能蛋白相接,并可用于发现与肿瘤缺陷有关的作用机制、新药物靶标和新的治疗方法.这些数据已存入Emory CTD2中心的portal网站,供大家分享.Emory中心是CTD2联盟一个重要组成部分,联盟内提供实时的数据分享,合作紧密.通过共同努力,笔者团队以及CTD2联盟的目标是发展新的一代肿瘤信号通路干扰药物,实现基因组学基础上的精准治疗.

As genomics advances reveal the cancer gene landscape,a daunting task is to translate these enormous volumes of information into efficacious genomics-based treatments for cancer patients.To address this challenge,the NCI Cancer Target Discovery and Development（CTD2）Network was created in the US.As a member of the CTD2 Network,the Emory CTD2 Center focuses specifically on the functional dimension of the cancer genome to establish re-wired protein-protein interaction（PPI）networks in cancer for therapeutic target discovery.To achieve this goal,high throughput screening technologies were utilized along with high throughput informatics approach.We aim to rapidly map molecular interactions among cancer associated proteins,leading to the generation of a cancer-associated PPI（OncoPPi）network.OncoPPi is a focused PPI resource that links cancer genes into a signaling network for discovery of PPI targets and network-implicated tumor vulnerabilities.This resource is accessible from the Emory OncoPPi portal.Emory＇s approach is an integral component of the CTD2 network,which allows timely data sharing and close collaboration.Together,we aim to develop the next generation of pathwayperturbation agents to selectively disrupt re-wired oncogenic signaling networks for genomics-directed precision medicine.