Developing novel RPPA for the detection of metastatic prostate cancer

开发新型 RPPA 用于检测转移性前列腺癌

基本信息

批准号：
9200292
负责人：
W. Andy Tao
金额：
$ 22.5万
依托单位：
TYMORA ANALYTICAL OPERATIONS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9200292
关键词：
Adopted Affinity Agreement Antibodies Automation Basic Science Binding Cell Culture Techniques Cell Extracts Chemicals Clinical Clinical Research Collaborations DU145 Detection Development Diagnosis Diagnostic Procedure Disease Exhibits Genetic Human Image Immobilization Indolent Ions Kinetics Malignant Neoplasms Malignant neoplasm of prostate Maps Measures Membrane Metals Metastatic Prostate Cancer Molecular Mus Nature Oncogenes PSA screening Pathway interactions Patients Phase Phospho-Specific Antibodies Phosphopeptides Phosphoproteins Phosphorylation Polymers Procedures Prognostic Marker Prostatic Neoplasms Protein Array Proteomics Pyroxylin Reagent Reproducibility Research Personnel Sampling Screening for Prostate Cancer Sensitivity and Specificity Signal Pathway Signal Transduction Signaling Molecule Small Business Technology Transfer Research Specificity Spottings Techniques Technology Testing Therapeutic Tissue Sample United States National Institutes of Health Xenograft procedure anticancer research base cancer heterogeneity cancer type clinical application combat cost cost effectiveness design experience improved individual patient innovation mouse model nanopolymer novel phase 1 study phase 2 study pre-clinical pre-clinical research protein profiling tool tumor

项目摘要

PROJECT SUMMARY Reverse-phase protein array (RPPA) has emerged as a promising antibody-based highly quantitative proteomic technology suitable for profiling proteins in hundreds to thousands of patient samples. The throughput, sensitivity, and cost effectiveness of RPPA, together with its ability to deal with minuscule sample amounts, have propelled applications of the technology in basic, preclinical and clinical research fields. The technology, which relies heavily on the paucity of high-quality monospecific antibodies, however, is only centered on detecting a few key signaling molecules due to limited availability of high quality phosphospecific antibodies. In this NIH STTR Phase I study, we will develop a novel RPPA platform based on metal ion-functionalized soluble nanopolymers into commercial products for sensitive, high throughput profiling of signaling molecules without the limitation of antibodies. The novel RPPA platform will be applied to distinguish aggressive from indolent human prostate tumors in xenograft mouse models. We hypothesis that prostate cancer can be classified by measuring phosphorylation changes on key oncogenes and thus a RPPA platform can be used as a discovery and preclinical tool to distinguish aggressive from indolent tumors. The following aims will be completed. Aim #1: Optimization of functionalized RPPA for capture and detection of phosphopropteins. Aim #2: Pathway-activation profiling in indolent and aggressive prostate cancer xenograft mouse models. By the completion of Phase I study, we expect that an analytical platform can be established with high sensitivity, wide dynamic range, excellent reproducibility, and affordable cost.

项目摘要反相蛋白阵列（RPPA）已成为一种有希望的基于抗体的高度定量蛋白质组学技术适用于数百至数千名患者样品中的蛋白质。这 RPPA的吞吐量，敏感性和成本效益，以及与微小的能力样本量，已经推动了该技术在基本，临床前和临床上的应用研究领域。这项技术在很大程度上依赖于高质量单特异性的技术然而，抗体仅集中于检测由于有限的几个键信号分子高质量磷酸抗体的可用性。在此NIH STTR I期研究中，我们将将基于金属官能化可溶性纳米聚合物的新型RPPA平台开发用于敏感的，高通量的信号分子的商业产品抗体的限制。新颖的RPPA平台将用于区分侵略性和异种移植小鼠模型中的浅薄人前列腺肿瘤。我们假设前列腺癌可以通过测量关键癌基因的磷酸化变化，从而分类可以用作发现和临床前工具，以区分侵略性和懒惰的肿瘤。这以下目标将完成。目标＃1：优化功能化的RPPA用于捕获和检测磷酸蛋白酶。目标＃2：懒惰和侵略性的途径激活分析前列腺癌异种移植小鼠模型。到完成第一阶段研究的完成，我们希望可以建立高灵敏度，广泛的动态范围，优秀的分析平台可重复性和负担得起的成本。