Profiling Cancer using Reverse-Phase NanoArrays

描述(由申请人提供)：这项建议描述了一项第一阶段研究，以测试使用超微型蛋白质纳米阵列分析癌前转化和对人类癌症活检样本进行治疗监测的可行性。Bioforce实验室公司将与FDA-NCI临床蛋白质组计划合作进行这项研究，该计划的目标是对癌症进展过程中发生的蛋白质组变化进行分类，并利用这些信息通过个性化的分子医学来革命性地诊断和治疗。这一目标需要一种可靠、经济有效的分析方法，这种方法可以从极其有限的患者组织中产生准确的蛋白质图谱。 在第一阶段，目前的反相微阵列技术将用于纳米阵列形式。我们将分析使用纯化的抗原和验证的抗体进行标记物检测的精密度、线性和限度。在第二阶段，我们将使用先前定义的食道癌系统来验证纳米阵列技术。这一阶段将利用实际激光捕获来自患者匹配的进展期食道癌的显微解剖细胞群。这些样本将由FDA-NCI临床蛋白质组学研究人员提供给BioForce。 第二阶段的研究将包括使用一组更大的标志物对更广泛的癌症进行筛查。我们预计，在大规模第二阶段研究中产生的实验数据将导致识别癌症特异的、临床相关的标志物和整个信号通路。这可能成为新的诊断和治疗方法的基础，这些方法将成为为肿瘤学市场构建商业诊断工具的基础，并将成为治疗医生治疗管理的组成部分。

DESCRIPTION (provided by applicant): This proposal describes a Phase I research study to test feasibility of using an ultra-miniaturized protein NanoArray for analysis of premalignant conversion and therapeutic monitoring in human cancer biopsy samples. BioForce Laboratory, Inc. will conduct this study in collaboration with the FDA-NCI clinical proteomics program, whose objective is to catalogue proteomic changes occurring during cancer I progression, and use this information to revolutionize diagnosis and treatment through individualized molecular medicine. This target requires the availability of a reliable, cost-effective assay that can generate accurate protein profiles from exceedingly limited quantities of patient tissue. In the first stage current reverse-phase microarray techniques wiII be adapted for use in the NanoArray format. We will analyze precision, linearity and limits of marker detection using purified antigen and validated antibodies. In the second stage we will validate the NanoArray technology using a previously defined esophageal cancer system. This stage will utilize actual laser capture microdissected cell populations derived from patient-matched, progressive stages of malignant esophageal cancer. These samples will be provided to BioForce from the FDA-NCI clinical proteomics researchers. Phase II studies will involve screening of a wider variety of cancers using a larger set of markers. We anticipate that experimental data generated in a large-scale Phase II study will lead to the identification of cancer-specific, clinically relevant markers and entire signal pathways. This could become the foundation for new diagnostic and therapeutic approaches that wilI be the basis for construction of commercial diagnostic tools for the oncology market and will be integral to therapeutic management by the treating physician.