CORE--CHEMOTHERAPY AND TOXICOLOGY

该核心组件包括实验室设施、设备和 这三个项目将共同参与计划。 其核心是理念上的服务导向。 其目标是提供 以及时、有效和具有成本效益的方式， 候选药物的抗肿瘤活性，可能处于不同的阶段， 在拟定的方案中。 评价范围可能从最初的 筛选（与相关标准试剂相比的细胞毒性）， 支持IND申请的评价（例如，剂量和治疗 调度优化）。 评价将以一系列不同的方式进行， 体外和体内模型被配置为提供标准化方法， 开发具有未知活性但足够灵活的试剂， 为代理商提供定制的方法，了解更多。 数据 从培养的一组人类肿瘤细胞系将提供额外的 体内模型（人肿瘤异种移植物）选择指南 药物活性的详细评价。 这些研究可以通过以下方式加以补充： 在常规鼠肿瘤模型中的评价。 这种方法，虽然 不是排他性的，强调发现和发展积极对抗 实体瘤 数据将以比较IC 50值表示 来自体外研究和临床相关终点（例如，治愈， 消退或治疗失败时间延长）。 将在所有研究中评估剂量-反应关系。 有限 并将进行初步毒理学评价。 使用这些 药物开发决策中的数据将是以下各方的合作努力： 核心组件负责人、核心共同负责人、单个项目 领导者和PI计划。

This core component is comprised of laboratory facilities, equipment, and services that will be shared by the three projects of the proposed program. The core is service-oriented in concept. Its objective will be to provide in a timely, efficient, and cost-effective manner the evaluation of the antitumor activity of candidate drugs that may be at various stages of development in proposed program. Evaluations may range from initial screening (cytotoxicity compared to relevant standard agents) to detailed evaluations in support of an IND application (e.g., dose and treatment schedule optimization). Evaluations will be conducted in an array of in vitro and in vivo models configured to provide a standardized approach to the development of agents with unknown activity but flexible enough to provide customized approaches for agents about which more is known. Data from a panel of human tumor cell lines in culture will provide additional guidance in the selection of in vivo models (human tumor xenografts) for detailed evaluation of drug activity. These studies may be complemented by evaluations in conventional murine tumor models. This approach, although not exclusive, emphasizes discovery an development of agents active against solid tumors. Data will be presented in terms of comparative IC50 values from in vitro studies and clinically relevant endpoints (e.g., cures, regressions, or prolonged time to treatment failure) from in vivo studies. Dose-response relationships will be assessed in all studies. Limited preliminary toxicological evaluations will also be conducted. Use of these data in drug development decision making will be a cooperative effort among the core component leader, the core co-leaders, the individual project leaders, and the program PI.