An integrated computational and functional genomics discovery engine for preclini

描述（由申请人提供）：靶向治疗代表了肿瘤治疗的未来。为此，我们最近在四个独立的环境中确定并随后验证了新的药物靶点，这些靶点对携带常见癌基因和肿瘤抑制基因突变的肿瘤有效且特异性。我们的功能遗传方法，基于合成致死率的遗传原理，利用最先进的高通量RNA干扰和小分子筛选平台，基因定义细胞系统以及患者来源的培养来发现靶标，先进的计算生物学方法使用公开可用的数据集来优先考虑靶标，以及患者来源的异种移植物来验证三个新靶标。通过这一整合发现引擎的开发和扩展，我们将生成几种主要癌基因/肿瘤抑制基因的金标准合成致死数据库，并确定三种主要癌症类型的新药物靶点。在不久的将来，这个管道可以用于迭代临床试验设计和个性化癌症治疗。

DESCRIPTION (provided by applicant): Targeted therapies represent the future of oncology treatment. Toward this end, we have recently identified and subsequently validated novel drug targets in four independent settings that are effective and specific to tumors bearing mutations in common oncogenes and tumor suppressor genes. Our functional genetic approach, based on the genetic principle of synthetic lethality, utilizes a state-of-the-art high-throughput RNA interference and small molecule screening platform, genetically defined cell systems as well as patient-derived cultures for target discovery, advanced computational biology methods using publically available datasets to prioritize targets, and patient-derived xenografts to validate thee novel targets. Through the development and expansion of this integrative discovery engine, we will generate a gold standard synthetic lethal database for several major oncogenes/tumor suppressor genes and identify novel drug targets for three major cancer types. In the very near future this pipeline could be utilized for iterative clinical trial design and personalized cancer treatment.