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: 8654308
• 负责人: TODD R. GOLUB
• 金额: $ 69.37万
• 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/8654308
• 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，特别是来源于上皮性癌症的肿瘤，表现出难以识别的全局基因组改变