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

基本信息

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
项目类别：
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

项目摘要

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）：恶病质是一种代谢浪费综合征，通常会影响癌症患者，占癌症死亡的25％。癌症恶病质的根本原因仍然未知，因此目前尚无对该疾病的有效治疗方法。我们已经开发了有史以来研究癌症恶病质的第一个实验系统，因此我们在这里建议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候选蛋白，我们将根据其在患者衍生的血浆样本中的差异丰度来进一步验证这些候选者，我们将在体外和体内验证它们。预计这些研究将导致发现恶氧乙干的生物学基础，从而为有效的治疗剂的发展建立了清晰的途径。