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

TAS::75 0849::WNT/卷曲和 HGF/C-MET 信号蛋白的 TAS 药效学测定

• 批准号: 8174110
• 负责人: ANU MATHEW
• 金额: $ 14.97万
• 依托单位: MESO SCALE DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8174110
• 关键词: Antineoplastic Agents; Biological Assay; Biopsy; Cell Line; Clinical; Clinical Trials; Collaborations; Development; Diagnostic; Evaluation; Malignant Neoplasms; Measurement; Measures; Molecular; Monitor; Pathway interactions; Patients; Pharmacodynamics; Phase; Plasma; Pre-Clinical Model; Proteins; Renal Cell Carcinoma; Reproducibility; Research; Sampling; Signal Pathway; Signaling Protein; Specimen; Technology; Therapeutic Agents; Tissues; Tumor Tissue; Universities; Vendor; Work; meetings; pre-clinical; reagent testing; response; tool; treatment effect; tumor; tumor xenograft

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.

将使用 Meso Scale Diagnostics (MSD) 多阵列技术开发针对 NCI 高优先级药效学目标的多重检测，以促进从单个肿瘤活检或替代组织样本中读取多个集成药效学读数。这些测定将适用于测量分子水平对治疗的反应以及治疗剂的临床前开发。将开发检测方法来评估与许多恶性肿瘤有关的 Wnt/Frizzled 和 HGF/c-Met 信号通路，包括肾细胞癌 (RCC)。这些测定将在临床前模型、特征细胞系、肿瘤异种移植组织和患者血浆样本中得到证实。在随后的第 2 阶段工作中，我们将与 NCI 合作，将优化的检测方法应用于患者样本。临床前样品将来自商业供应商或由我们的合作者 Drs. 提供。 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（包括测量总信号蛋白和磷酸化信号蛋白）、精湛的测定灵敏度、最少的样品需求、宽动态范围以及易于测定的可扩展性，使该技术非常适合实现 NCI 的分子药效学应用目标。这项研究将为在临床试验中评估和验证新的抗癌药物以及最终临床用于监测治疗提供有价值的工具。