DCTD In Vivo Preclinical Testing

体内临床前支持实验室-体内临床前支持小组通过体内潜在抗癌药物的检测为生物学检测分支提供支持。在中空纤维试验中评价提交给DTP的新药，以使用最少量的试验材料以及最少数量的动物评估其体内活性的潜力。然后在适当的啮齿动物肿瘤模型（例如，免疫缺陷小鼠中的异种移植物或同系小鼠中的啮齿动物肿瘤），其中除了抗肿瘤作用之外，还检查了施用途径、剂量和给药方案。沿着疗效研究，该小组通过评价化合物对啮齿类动物中生长的肿瘤的药效学（PD）作用，为0期和CBC计划提供支持。该小组是DTP抗癌药物开发工作、0期PD标志物验证工作和CBC体内疗效评价途径的组成部分。 化合物配方和化合物筛选-化合物配方和化合物筛选组通过制备用于体内疗效模型评估的测试试剂（包括中空纤维和异种移植研究），为生物测试分支提供支持。该小组负责保存供试制剂的库存，并准确称重和溶解供试材料进行试验。此外，他们还根据需要确定试验药物在拟定溶媒中的溶解度。该小组还为2008年开展的新的复方药物筛选工作提供技术支持。这些试验提供了来自临床批准的药物与第二种临床批准的药物或临床试验中的药物组合的研究的体外疗效数据。这些试验在3种不同的细胞系中使用3种剂量水平的每种测试试剂进行。

In Vivo Preclinical Support Laboratory - The In Vivo Preclinical Support group provides support to the Biological Testing Branch through its testing of potential anticancer agents in vivo. New agents submitted to the DTP are evaluated in the hollow fiber assay to assess their potential for in vivo activity using minimal amounts of test material as well as a minimal number of animals. Agents that are active in this assay are then tested in appropriate rodent tumor models (e.g., xenografts in immunodeficient mice or rodent tumors in syngeneic mice) where the route of administration, dose, and dose schedules are examined, in addition to the antitumor effect. Along with efficacy studies, this group provides support to the Phase 0 and CBC initiatives through evaluation of the pharmacodynamic (PD) effect of compounds on tumors growing in rodent species. This group is an integral part of the DTP anticancer drug development effort, the Phase 0 PD marker validation effort, and the CBC in vivo efficacy evaluation pathway. Compound Formulation & Compound Screening - The Compound Formulation & Compound Screening group provides support to the Biological Testing Branch through its preparation of test agents for assessment in the in vivo efficacy models including the hollow fiber and xenograft studies. This group maintains an inventory of test agents and accurately weighs and solubilizes the test material for testing. In addition, they determine the solubility of test agents in proposed vehicles as needed. This group also provides the technical support for the new combination drug screening effort undertaken in 2008. These assays provide in vitro efficacy data from studies in which a clinically approved agent is combined with a second clinically approved agent or an agent in clinical trials. These assays are conducted in 3 distinct cell lines using 3 dose levels of each test agent.