CORE--CHEMOTHERAPY AND TOXICOLOGY

申请者描述：(由申请者提供)此核心组件是 由将共享的实验室设施、设备和服务组成 由四个项目提出方案。核心是面向服务的 概念。其目标将是提供及时、高效和 以经济有效的方式评价候选药物的抗肿瘤活性 在拟议的计划中，可能处于不同开发阶段的药物。 评估的范围可能从最初的筛查(与 相关标准代理)对支持IND的详细评估 应用(例如，剂量和治疗计划的优化)。评估 将在一系列体外和体内模型中进行，配置为 提供了一种开发未知代理的标准化方法 活动，但足够灵活，可在选择时提供额外指导 用于药物详细评估的体内模型(人肿瘤异种移植) 活动。这些研究可能会得到常规评估的补充。 小鼠肿瘤模型。这种方法虽然不是排他性的，但强调了 抗实体瘤活性药物的发现与发展。数据将是 以来自体外研究的比较IC50值和 临床相关的终点(例如，治愈、退化或延长的时间 治疗失败)。剂量-反应关系将是 在所有研究中进行了评估。这些数据在药物开发决策中的应用 这将是核心组件领导者之间的合作努力 个人项目负责人，以及项目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.