TAS::75 0849::TAS PHARMACODYNAMIC ASSAYS FOR WNT/FRIZZLED AND HGF/C-MET SIGNALIN

NCI高优先级药效学靶点的多重检测将使用Meso Scale Diagnostics (MSD) Multi-Array技术开发，以促进单个肿瘤活检或替代组织标本的多重综合药效学读数。这些检测将适用于与临床前治疗剂开发相结合的分子水平治疗反应的测量。将开发检测方法来评估Wnt/ frizzed和HGF/c-Met信号通路与许多恶性肿瘤，包括肾细胞癌（RCC）有关。这些检测将在临床前模型、特征细胞系、肿瘤异种移植组织和患者血浆样本中进行验证。与NCI合作，优化的检测方法将在随后的2期工作中应用于患者样本。临床前样品将来自商业供应商或由我们的合作者dr。Mier和Panka（哈佛大学）正在进行的癌症治疗效果研究。MSD的多重功能（包括测量总和磷酸化信号蛋白），精致的分析灵敏度，最小的样品要求，宽动态范围和易于分析可扩展性，使该技术非常适合实现NCI的分子药理学应用目标。这项研究将为临床试验中评估和验证新的抗癌药物提供有价值的工具，并最终用于临床监测治疗。

Multiplexed assays for pharmacodynamic targets of high priority for the NCI will be developed using Meso Scale Diagnostics' (MSD) Multi-Array technology to facilitate multiple integrated pharmacodynamic readouts from a single tumor biopsy or surrogate tissue specimen. These assays will be suitable for measurement of molecular-level responses to treatment in conjunction with preclinical development of therapeutic agents. Assays will be developed to evaluate the Wnt/Frizzled and HGF/c-Met signaling pathways implicated in many malignancies, including renal cell carcinoma (RCC). These assays will be demonstrated in pre-clinical models, characterized cell lines, tumor xenograft tissues, and patient plasma samples. Optimized assays will be applied to patient samples in subsequent Phase 2 work, in collaboration with the NCI. Pre-clinical samples will be from commercial vendors or provided by our collaborators, Drs. Mier and Panka (Harvard University) from ongoing studies on treatment effects in cancer. MSD's multiplex capability (including measuring total and phosphorylated signaling proteins), exquisite assay sensitivity, minimal sample requirement, wide dynamic ranges, and ease of assay scalability, make this technology ideally suited to achieving the NCI's objectives for molecular pharmacodynamic applications. This research will provide valuable tools to evaluate and validate new anti-cancer agents in clinical trials and for eventual clinical use to monitor treatment.