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

描述(申请人提供)：恶病质是一种代谢衰竭综合征，通常影响癌症患者，占癌症死亡人数的25%。癌症恶病质的根本原因尚不清楚，因此目前还没有有效的治疗方法。我们已经开发了第一个研究癌症恶病质的实验系统，因此我们建议在这里使用该系统来发现导致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，我们将根据患者来源的血浆样本中它们的不同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开辟一条明确的道路。

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.