Developmental Therapeutics (DT) Program

项目摘要/摘要(发展治疗学) 发展治疗(DT)计划的成员使用UMCCC取得的突破性见解 基础科学计划推动发现一流的小分子抗癌药物，这些药物可以 进入生物标记物驱动的临床试验。该计划作为调查人员的论坛，与共享 对新靶点、药物、治疗组合或基于天然产品的临床前开发感兴趣 干扰蛋白质-蛋白质相互作用、抑制激酶活性、靶向表观遗传修饰物或 起辐射敏感剂的作用。DT计划由来自18个部门和5个部门的31名成员组成 密歇根大学的学校。年度直接研究资助总额为1520万美元，其中410万美元(27%) 来自NCI的300万美元(19%)来自NIH的其他支持，370万美元(24.2%)来自其他同行审查的来源。在.期间 上一个资助期，并与结构和药物筛选以及 药代动力学共享资源，DT计划成员发表了547篇文章，其中22.1%是 方案内和35.8%是方案间。为了进一步推动这些进展，DT计划的研究正在 重点关注以下一个或多个具体目标：1)验证可服从的新的癌症靶点 到药物干预，2)治疗药物和潜力的发现、优化和评估 临床相关临床前模型系统中反应的生物标记物，以及3)临床前研究进展 通过DT之间的结构化合作对生物标记物启用的临床试验进行概念验证研究 计划成员和基于TACR的临床研究团队。通过将临床研究人员纳入 临床前研究的设计在前期IND阶段，DT计划寻求简化临床药物 发展的同时提高了临床成功的可能性。 1“ “

PROJECT SUMMARY/ABSTRACT (DEVELOPMENTAL THERAPEUTICS) Members of the Developmental Therapeutics (DT) Program use breakthrough insights made in the UMCCC basic science programs to drive the discovery of first-in-class small molecule anticancer agents that can be advanced into biomarker-driven clinical trials. The Program serves as the forum for investigators with shared interest in pre-clinical development of novel targets, agents, therapeutic combinations or natural product-based drugs that either perturb protein-protein interactions, inhibit kinase activity, target epigenetic modifiers or function as radiation sensitizers. The DT Program comprises 31 members from 18 departments and five schools across the University of Michigan. Total annual direct research support is $15.2M, with $4.1M (27%) from the NCI, $3M (19%) from other NIH support and $3.7M (24.2%) from other peer-reviewed sources. During the last funding period, and in close collaboration with the Structure and Drug Screening as well as Pharmacokinetics Shared Resources, DT Program members authored 547 publications, of which 22.1% are intra-programmatic and 35.8% are inter-programmatic. To further these advances, DT Program research is focused on one or more of the following Specific Aims: 1) validation of novel cancer targets that are amenable to pharmacological intervention, 2) discovery, optimization and evaluation of therapeutic agents and potential biomarkers of response in clinically relevant preclinical model systems, and 3) advancement of preclinical proof-of-concept studies into biomarker-enabled clinical trials through structured collaborations between DT Program members and TACR-based clinical investigator teams. By incorporating clinical investigators in the design of preclinical studies at the pre-IND stage, the DT Program seeks to streamline clinical drug development while improving the likelihood of clinical successes. 1" "