首页> 外国专利> ONCOGENOMICS-BASED RNAi SCREEN AND USE THEREOF TO IDENTIFY NOVEL TUMOR SUPPRESSORS

ONCOGENOMICS-BASED RNAi SCREEN AND USE THEREOF TO IDENTIFY NOVEL TUMOR SUPPRESSORS

机译:基于肿瘤基因组学的RNAi屏幕并用于鉴定新的肿瘤抑制因子

摘要

In some aspects, the invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both and by transplanting the resulting hepatocytes into a recipient non-human animal.;The present invention also provides methods for identifying and validating tumor suppressor genes by screening pools of shRNAs that target genomic regions deleted in human cancers, such as human hepatocellular carcinomas. The present invention also provides validated tumor suppressor genes, and methods of inhibiting cell proliferation and/or tumor growth, for example by expression of such tumor suppressor genes.
机译:在一些方面,本发明提供了用于肝细胞癌的遗传上易处理的原位非人动物模型。该模型尤其可用于了解肝癌的分子机制,了解导致化学耐药性或不良预后的遗传改变,以及用于识别和评估针对肝细胞癌的新疗法。本发明的肝癌模型是通过改变肝细胞以增加癌基因表达,降低肿瘤抑制基因表达或两者并通过将所得肝细胞移植到非人类动物体内而制得的。本发明还提供了鉴定和验证方法。通过筛选针对人类癌症(例如人类肝细胞癌)中缺失的基因组区域的shRNA池,筛选出抑癌基因。本发明还提供了有效的肿瘤抑制基因,以及例如通过表达这种肿瘤抑制基因来抑制细胞增殖和/或肿瘤生长的方法。

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