Cancer dependencies associated with genomic alterations and targeted by small mol

癌症依赖性与基因组改变相关并通过小分子靶向

基本信息

批准号：
8657018
负责人：
STUART L SCHREIBER
金额：
$ 110.45万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8657018
关键词：
Alleles Antineoplastic Agents BCL2 gene Biological Markers Cancer Biology Cancer Patient Cancer cell line Caring Categories Cell Line Cells Chromatin Clinical Code Collaborations Combined Modality Therapy Communities Complementary DNA Computing Methodologies Data Data Analyses Data Sources Databases Dependency Disease Drug Combinations Drug Targeting Drug resistance Elements Ensure Enzymes Foundations Gene Expression Alteration Generations Genes Genetic Genetic Markers Genomics Glucocorticoid Receptor Health Human Individual Institutes Instruction KRAS2 gene Link MEKs Malignant Neoplasms Measures Medicine Mining Mutation Oncogenes Oncogenic Pathway interactions Pharmaceutical Preparations Phase Proteins RNA Interference Research Resistance Resources Science Source Sum Testing The Cancer Genome Atlas War base cancer cell cancer genetics cancer genome cancer genomics combination cancer therapy human FRAP1 protein improved inhibitor/antagonist insight meetings mouse model mutant novel overexpression patient population public health relevance research study resistance mechanism response small molecule tool tumor

项目摘要

DESCRIPTION (provided by applicant): Drugs that target oncogene- or non-oncogene-based dependencies acquired by cancers as a result of specific genomic alterations can yield high clinical response rates, although current drugs in this category benefit only a small fraction of cancer patients and the beneficial responses are not always durable. This project aims to discover drug-targetable dependencies for a wide range of cancer genomic alterations and identify the combinations of drugs that can avoid or overcome resistance. As part of the five-center and now nine-center CTD2 Network, we applied quantitative genomic cancer cell-line profiling to build an interactive resource for identifying cancer genetic dependencies targeted by small molecules. We made all aspects of this resource available to the cancer community through a public database, interactive data-analysis tools, code, and instructions that guide users through potentially confounding data- analysis issues. We now propose to advance the resource substantially in ways that enhance other Network research and impact the health of cancer patients. The project will integrate small-molecule and RNAi data from genomic cancer cell-line profiling within the interactive resource and discover dependencies targeted by single agents. It will also identify and test hypotheses suggested by the interactive resource about cancer genetic dependencies targeted by small molecules. Finally, the project will identify combinations of small- molecule agents that target oncogene or non-oncogene dependencies in cancer cells and that avoid or overcome drug resistance seen with single agents.

描述（由申请人提供）：靶向癌基因或非癌基因依赖性的药物，由于特定的基因组改变而获得的癌症获得的依赖性可以产生较高的临床反应率，尽管该类别中的当前药物仅受益于一小部分癌症患者，而有益的反应并非总是耐用。该项目旨在发现针对广泛的癌症基因组改变的可靶向依赖性，并确定可以避免或克服耐药性的药物组合。作为五个中心和现在的9个中心CTD2网络的一部分，我们应用了定量的基因组癌细胞线分析，以建立一种交互式资源来识别小分子靶向的癌症遗传依赖性。我们通过公共数据库，交互式数据分析工具，代码和指令使癌症社区的所有方面都可以使用，从而引导用户可能会混淆数据分析问题。现在，我们建议以增强其他网络研究并影响癌症患者健康的方式基本上推进资源。该项目将从基因组癌细胞系分析中整合互动资源中的小分子和RNAi数据，并发现单个药物针对的依赖项。它还将识别和检验由小分子针对的癌症遗传依赖性的互动资源提出的假设。最后，该项目将确定癌细胞中靶向癌基因或非生物依赖性的小分子剂的组合，并避免或克服单个药物看到的耐药性。