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.
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