CORE--CHEMOTHERAPY AND TOXICOLOGY

申请人描述：（由申请人提供）该核心组件是 由共享的实验室设施、设备和服务组成 四个项目的建议方案。 核心是面向服务， 概念. 其目标将是提供及时、有效和 以成本效益的方式评价候选物的抗肿瘤活性 在拟议的计划中可能处于不同开发阶段的药物。 评价的范围可以从初始筛选（细胞毒性比较， 相关标准制剂）进行详细评价，以支持IND 应用（例如，剂量和治疗方案优化）。 评价 将在体外和体内模型阵列中进行， 提供了一个标准化的方法来开发未知的代理商， 活动，但足够灵活，以提供额外的指导，在选择 用于详细评价药物的体内模型（人肿瘤异种移植物） 活动 这些研究可以通过常规评估加以补充。 鼠肿瘤模型。 这种方法，虽然不是排他性的，强调 发现和开发对实体瘤有活性的药物。 数据将 以来自体外研究的比较IC 50值表示， 临床相关终点（例如，治愈、退化或延长时间， 治疗失败）。 剂量-反应关系将是 在所有研究中进行评估。 在药物开发决策中使用这些数据 这将是核心组件领导者， 个人项目负责人和项目PI。

APPLICANT'S DESCRIPTION: (provided by Applicant) This core component is composed of laboratory facilities, equipment, and services that will be shared by the four 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 the 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 provided a standardized approach to the development of agents with unknown activity but flexible enough to 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 and 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. Use of these data in drug development decision making will be a cooperative effort among the core component leader, the individual project leaders, and the program PI.