PQB-3: Discovery and validation of the driving mediators of cancer cachexia

PQB-3：癌症恶病质驱动介质的发现和验证

• 批准号: 8792102
• 负责人: TODD R. GOLUB
• 金额: $ 55.44万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-17 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8792102
• 关键词: Accounting; Adipose tissue; Affect; Animal Model; Antibodies; Automobile Driving; Biochemical; Biological; Biological Assay; Biological Models; Biology; Cachexia; Cancer Etiology; Cancer Patient; Cancer cell line; Candidate Disease Gene; Cell Line; Cessation of life; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Complex; Conditioned Culture Media; Development; Disease; Enzyme-Linked Immunosorbent Assay; Event; Fatty acid glycerol esters; Fractionation; Future; Genes; Glare; Hand; Human; Immunoassay; In Vitro; Knock-out; Label; Laboratories; Lead; Letters; Liver Dysfunction; Malignant Neoplasms; Mediating; Mediator of activation protein; Memorial Sloan-Kettering Cancer Center; Metabolic; Metabolic syndrome; Metabolism; Methods; Molecular Weight; Muscle; Muscle Cells; Muscle Fibers; Myocardium; Patients; Phenotype; Plant Roots; Plasma; Positioning Attribute; Process; Proteins; Proteomics; Recruitment Activity; Research; Role; Sampling; Serum; Skeletal Muscle; System; Techniques; Testing; Therapeutic; Tumor-Secreted Protein; Validation; Wasting Syndrome; base; cancer type; clinical care; clinically relevant; effective therapy; functional genomics; gain of function; in vivo; inhibitor/antagonist; loss of function; metabolomics; multiple reaction monitoring; neoplastic cell; prevent; public health relevance; research study; small molecule; therapeutic development; tumor; wasting

DESCRIPTION (provided by applicant): Cachexia is a metabolic wasting syndrome that commonly affects cancer patients, and accounts for as many as 25% of cancer deaths. The root causes of cancer cachexia remain unknown, and as such there are presently no effective treatments for the disorder. We have developed the first-ever experimental system to study cancer cachexia, and we therefore propose here to use the system to discover the proteins secreted by tumors that cause the cachexia phenotype. We will use advanced proteomic approaches to identify high priority candidate proteins, and we will further validate those candidates based on their differential abundance in patient-derived plasma samples, and we will functionally validate them both in vitro and in vivo. These studies are expected to lead to the discovery of the biological basis of cachexia, and thereby establish a clear path toward the development of effective therapeutics.

描述（由申请人提供）：恶病质是一种代谢性消耗综合征，通常影响癌症患者，占癌症死亡的25%。癌症恶病质的根本原因仍然未知，因此目前没有有效的治疗方法。我们已经开发了有史以来第一个研究癌症恶病质的实验系统，因此我们在这里提出使用该系统来发现引起恶病质表型的肿瘤分泌的蛋白质。我们将使用先进的蛋白质组学方法来识别高优先级的候选蛋白质，我们将根据这些候选蛋白质在患者血浆样本中的差异丰度进一步验证这些候选蛋白质，我们将在体外和体内对它们进行功能验证。这些研究有望发现恶病质的生物学基础，从而为开发有效的治疗方法奠定明确的道路。