Individualized network-based drug repositioning infrastructure for precision oncology in the panomics era
Individualized network-based drug repositioning infrastructure for precision oncology in the panomics era
复制标题
泛组学时代精准肿瘤学的个性化网络药物重新定位基础设施
DOI：
10.1093/bib/bbw051
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发表时间：
2017-07-01
影响因子：
9.5
通讯作者：
Wei, Yuquan
中科院分区：
文献类型：
--
作者：
Cheng, Feixiong;Hong, Huixiao;Wei, Yuquan
新一代测序技术的进步已经在一些国家和国际癌症基因组计划中产生了支持大量体细胞改变的数据，例如癌症基因组图谱和国际癌症基因组联盟。这些癌症基因组学数据促进了一种新的肿瘤药物发现范式的革命，从候选靶点或基因研究转向针对临床相关的驱动突变或精确癌症治疗的分子特征。这侧重于确定最适当的靶向治疗，以个别患者具有特定的遗传特征或分子特征。然而，传统的实验方法用于开发针对临床相关驱动突变的新化学实体是昂贵和高风险的。药物重新定位，也被称为药物重新定位、重新任务或重新分析，已被证明是一种很有前途的药物发现和开发策略。近年来，已经提出了用于肿瘤药物重新定位和药物基因组学生物标志物识别的计算技术和方法，但总体进展仍有待观察。在本文中，我们将重点介绍基于个体化网络的药物重新定位方法的新进展和进展，通过针对临床相关驱动事件或从癌症全组学数据中获得的分子特征来开发精确的肿瘤药物治疗（如单人试验），以充分实现精准医学的承诺。我们讨论了精确肿瘤学的几个潜在挑战（例如肿瘤异质性和癌症亚克隆）。最后，我们强调了在功能基因组学时代，通过生物治疗（如基因治疗和免疫治疗）靶向“不可药物”癌症基因组的精准肿瘤药物发现的几个新方向。
Advances in next-generation sequencing technologies have generated the data supporting a large volume of somatic alterations in several national and international cancer genome projects, such as The Cancer Genome Atlas and the International Cancer Genome Consortium. These cancer genomics data have facilitated the revolution of a novel oncology drug discovery paradigm from candidate target or gene studies toward targeting clinically relevant driver mutations or molecular features for precision cancer therapy. This focuses on identifying the most appropriately targeted therapy to an individual patient harboring a particularly genetic profile or molecular feature. However, traditional experimental approaches that are used to develop new chemical entities for targeting the clinically relevant driver mutations are costly and high-risk. Drug repositioning, also known as drug repurposing, re-tasking or re-profiling, has been demonstrated as a promising strategy for drug discovery and development. Recently, computational techniques and methods have been proposed for oncology drug repositioning and identifying pharmacogenomics biomarkers, but overall progress remains to be seen. In this review, we focus on introducing new developments and advances of the individualized network-based drug repositioning approaches by targeting the clinically relevant driver events or molecular features derived from cancer panomics data for the development of precision oncology drug therapies (e.g. one-person trials) to fully realize the promise of precision medicine. We discuss several potential challenges (e.g. tumor heterogeneity and cancer subclones) for precision oncology. Finally, we highlight several new directions for the precision oncology drug discovery via biotherapies (e.g. gene therapy and immunotherapy) that target the 'undruggable' cancer genome in the functional genomics era.