Integrated Translational Genoproteomics Center at Washington University

华盛顿大学综合转化基因蛋白质组学中心

• 批准号: 8845178
• 负责人: CHRISTINE H CHUNG
• 金额: $ 57.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-02 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8845178
• 关键词: Acute; Address; Aftercare; Antibodies; Biological; Biological Assay; Biological Markers; Biological Pharmacology; Biology; Clinical; Clinical Trials; Collaborations; Colon Carcinoma; Complement; Conduct Clinical Trials; Consent; Correlative Study; Country; DNA Sequence; Data; Data Analyses; Development; Diagnosis; Disease; Disease Outcome; Drug effect disorder; Eligibility Determination; Epithelial; Etiology; Event; Formalin; Gene Expression Profile; Generations; Genome; Genomics; Goals; Grant; Head and Neck Cancer; Heterogeneity; High-Throughput Nucleotide Sequencing; Hour; Individual; Institutes; Investigation; Investments; Laboratories; Letters; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Mass Spectrum Analysis; Massive Parallel Sequencing; Medical; Molecular; Mutation; Neoadjuvant Therapy; Operative Surgical Procedures; Organ; Outcome; Pathology; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Phosphotransferases; Pilot Projects; Postdoctoral Fellow; Prospective Studies; Protein Array; Proteome; Proteomics; RNA Sequences; Rectal Cancer; Reporting; Research; Research Personnel; Sampling; Science; Signal Transduction; Site; Specimen; Speed; Standardization; Stratification; Stream; Structure; Surveys; Systemic Therapy; Technical Expertise; Technology; Testing; The Cancer Genome Atlas; Therapeutic; Translating; Tumor Biology; Tumor Tissue; Universities; Validation; Washington; base; cancer proteomics; chemoradiation; chemotherapy; clinical investigation; clinical practice; data acquisition; design; genetic information; genetic regulatory protein; genome sequencing; improved; innovation; instrumentation; malignant breast neoplasm; new therapeutic target; next generation; oncology; precision medicine; programs; prospective; protein aminoacid sequence; response; screening; transcription factor; transcriptome sequencing; translational medicine; treatment response; tumor

DESCRIPTION (provided by applicant): Next Generation cancer 'omics technologies are revolutionizing our understanding of cancer, but our approaches to clinical investigation have not kept pace. The Cancer Genome Atlas (TCGA) is delivering an impressive body of data and technical advances in data analysis, but is analytically limited by the uncontrolled clinical settings in which the samples were accrued. We therefore propose to match the technical expertise of The Genome Institute at Washington University with the accrual power and clinical expertise of the NRG cooperative group to provide clinical and biological annotation for the vast quantities of new data generated by high-throughput sequencing platforms. We also anticipate major technical advances in the proteomics field as a result of the investment by the NCI in the Clinical Proteomics Tumor Analysis Consortium (CPTAC). We therefore propose the "Integrated Translational Genoproteomlcs Center" (ITGC) that will nucleate a concerted effort to integrate DNA, RNA and Peptide sequencing into NRG clinical trials to a) increase our biological understanding of common epithelial cancers, b) develop biomarkers of treatment response and c) identify new therapeutic targets. This proposal includes plans for five proteogenomic pilot projects with NRG Oncology In breast cancer, head and neck cancer, ovarian cancer, rectal cancer and prostate cancer. The aims of these demonstration projects are to fully integrate proteogenomics into prospective clinical trials of preoperative systemic therapy, to develop genoproteomic assays for clinical trial eligibility and stratification and to integrate mass-spectrometry-based and reverse phase protein array-based (RPPA) proteomics into the existing genomic sample analysis pipeline. Our strategic objective is to bring comprehensive discovery science into the cooperative group setting. This will drive the NRG Oncology organ site committees to more deeply appreciate the fundamental biology that underlies the diseases that they treat and should ultimately raise the quality of the clinical trial hypotheses that are pursue. RELEVANCE: The integration of DNA, RNA and Peptide sequencing-based discovery science into cooperative group trials is our goal. This will stimulate biomarker research that will drive te development of laboratory tests required for our long-term goal of a tumor etiology-matched therapeutics program that improves outcomes for a broad spectum of patients diagnosed with common epithelial malignancies.

描述（由申请人提供）：下一代癌症组学技术正在彻底改变我们对癌症的理解，但我们的临床研究方法尚未跟上步伐。癌症基因组图谱（TCGA）在数据分析方面提供了令人印象深刻的数据和技术进步，但在分析上受到样本积累的不受控制的临床环境的限制。因此，我们建议将华盛顿大学基因组研究所的技术专长与NRG合作组的累积能力和临床专长相匹配，为高通量测序平台产生的大量新数据提供临床和生物学注释。我们还预计，由于NCI对临床蛋白质组学肿瘤分析联盟（CPTAC）的投资，蛋白质组学领域将取得重大技术进步。因此，我们提出了“整合翻译基因蛋白组学中心”（ITGC），该中心将协同努力将DNA、RNA和肽测序整合到NRG临床试验中，以a）增加我们对常见上皮癌的生物学理解，B）开发治疗反应的生物标志物，以及c）鉴定新的治疗靶点。该提案包括与NRG肿瘤学在乳腺癌、头颈癌、卵巢癌、直肠癌和前列腺癌方面开展五个蛋白基因组学试点项目的计划。这些示范项目的目的是将蛋白质组学完全整合到术前系统治疗的前瞻性临床试验中，开发用于临床试验资格和分层的基因蛋白质组学测定，并将基于质谱和基于反相蛋白质阵列（RPPA）的蛋白质组学整合到现有的基因组样本分析管道中。我们的战略目标是将综合发现科学纳入合作组设置。这将推动NRG肿瘤学器官研究中心委员会更深入地了解他们所治疗疾病的基础生物学，并最终提高所追求的临床试验假设的质量。 相关性：将基于DNA、RNA和肽测序的发现科学整合到合作组试验中是我们的目标。这将刺激生物标志物的研究，这将推动我们的肿瘤病因匹配治疗计划的长期目标所需的实验室测试的发展，该计划改善了诊断为常见上皮恶性肿瘤的广泛患者的结局。