The Dana-Farber Cancer Institute Cancer Target Discovery and Development Center

丹娜—法伯癌症研究所癌症靶标发现和开发中心

• 批准号: 8494195
• 负责人: TODD R. GOLUB
• 金额: $ 72.59万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 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/8494195
• 关键词: Animals; Atlas of Cancer Mortality in the United States; Biochemical Pathway; Bioinformatics; Biological Assay; CRKL gene; Cell model; Clinic; Clinical; Collection; Colon; Colon Carcinoma; Communities; Dana-Farber Cancer Institute; Data; Data Set; Dependency; Development; Diagnostic; Epithelial; Exhibits; Experimental Models; Foundations; Frequencies; Future; GAB2 gene; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic Screening; Genome; Genomic Instability; Genomics; Genotype; Glioblastoma; Goals; Health; Human; Image; In Vitro; Information Dissemination; Investigator-Initiated Research; Investments; Lead; Libraries; Link; Maintenance; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Mammalian Cell; Measures; Methodology; Methods; Mutate; Mutation; Oncogenes; Oncogenic; Open Reading Frames; Output; Ovarian; Pathway interactions; Play; Population; Proteins; Proteomics; RNA Interference; Reagent; Recurrence; Research Infrastructure; Research Personnel; Role; Signal Pathway; Signal Transduction; System; Technology; The Cancer Genome Atlas; Therapeutic; Time; Translating; Translations; Tumor Suppressor Genes; Tumorigenicity; Work; anticancer research; base; cancer genome; cancer initiation; cancer type; cell transformation; colon cancer cell line; functional genomics; gain of function; gene function; high throughput technology; in vivo; insight; loss of function; novel; novel therapeutic intervention; programs; response; small hairpin RNA; therapeutic target; tool; translational study; tumor; tumor initiation; tumor microenvironment; tumorigenesis; validation studies

DESCRIPTION (provided by applicant): Most human tumors, particularly those derived from epithelial cancers, exhibit global genomic alterations that make it difficult to identify mutations critical for cell transformation and to define the consequences of specific cancer associated mutations. Recent advances in sequencing technologies and comprehensive methods to map cancer-associated amplicons and deletions now make it possible to identify all of the genetic alterations harbored by a particular tumor, and large-scale efforts such as TCGA to apply these technologies have already begun to provide comprehensive views of cancer genomes. Despite these important advances, a critical bottleneck in translating these discoveries into therapies that will enter the clinic remais the functional characterization of genes as potential therapeutic targets. Specifically, although the identification of genes that are mutated in a substantial fraction of particular cancer types is an essential first step, the parallel development of efficient methods to annotate the function of cancer-associated genes is necessary to distill promising candidate cancer targets from this structural description of cancer genomes. Thus, functional annotation of cancer genes will identify those genes whose protein products are essential for tumor initiation or maintenance and will provide critical insights into the biochemical pathways that ar dysregulated in these same cancers. This information will accelerate the development of new molecularly targeted therapeutics. In this application, we propose use these studies as a foundation to establish the Dana- Farber Cancer Institute Cancer Target Discovery and Development Center. This Center will focus on the use of high throughput genetic and bioinformatic approaches to identify and credential oncogenes and co-dependencies in three cancers (GBM, ovarian, and colon) in vitro and in vivo. We will make the outputs of these studies (data and methodologies) freely available to the scientific community and intend to participate in CTDD Network projects throughout the time frame of this project. We anticipate that this Center will provide the cancer research community with information tht will facilitate the prioritization of targets based on both genomic and functional evidence, inform the most appropriate genetic context for downstream mechanistic and validation studies and facilitate the translation of this information into therapeutics and diagnostis.

描述（由申请人提供）：大多数人类肿瘤，特别是源自上皮癌的肿瘤，表现出全局基因组改变，使得难以识别 对细胞转化至关重要的突变，并确定特定癌症的后果 相关突变 测序技术和绘制癌症相关扩增子和缺失的综合方法的最新进展现在使得鉴定特定肿瘤所包含的所有遗传改变成为可能，大规模的努力，如TCGA应用这些技术已经开始提供癌症基因组的全面视图。 尽管取得了这些重要进展，但将这些发现转化为将进入临床的疗法的关键瓶颈仍然是作为潜在治疗靶点的基因的功能表征。具体地说，虽然在特定的基因中的很大一部分突变的基因的鉴定是不可能的。 癌症类型是必不可少的第一步，同时开发有效的方法来注释癌症相关基因的功能是必要的，以提取有希望的候选基因。 癌症靶点来自癌症基因组的结构描述。因此，癌症基因的功能注释将识别其蛋白产物对于肿瘤起始或维持是必需的那些基因，并且将提供对在这些相同癌症中失调的生化途径的关键见解。这些信息将加速新的分子靶向治疗的发展。 在本申请中，我们建议使用这些研究作为基础，建立达纳-法伯癌症研究所癌症靶点发现和开发中心。 该中心将专注于使用高通量遗传和生物信息学方法在体外和体内识别和鉴定三种癌症（GBM，卵巢和结肠）中的癌基因和共依赖性。我们将向科学界免费提供这些研究的成果（数据和方法），并打算在该项目的整个时间范围内参与CTDD网络项目。 我们预计，该中心将为癌症研究界提供信息，促进基于基因组和功能证据的靶点优先排序，为下游机制和验证研究提供最合适的遗传背景，并促进将这些信息转化为治疗和诊断。