Developmental Therapeutics (DT) Program

项目总结/摘要（药物治疗） 发展治疗学（DT）计划的成员使用UMCCC中取得的突破性见解 基础科学计划，以推动发现一流的小分子抗癌药物， 进入生物标志物驱动的临床试验。该计划作为研究人员的论坛， 对新靶点、药剂、治疗组合或基于天然产物的药物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、靶向表观遗传修饰剂或 作为辐射敏化剂。DT计划由来自18个部门和5个部门的31名成员组成 密歇根大学的所有学校。每年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%）来自其他NIH支持，370万美元（24.2%）来自其他同行评审来源。期间 在最后一个资助期，并与结构和药物筛选以及 药代动力学共享资源，DT项目成员撰写了547篇出版物，其中22.1%是 35.8%为方案内，35.8%为方案间。为了进一步推动这些进步，DT计划的研究是 专注于以下一个或多个特定目标：1）验证新的癌症靶点， 药物干预，2）发现，优化和评价治疗药物和潜在的 临床相关的临床前模型系统中的反应生物标志物，和3）临床前模型系统的进展， 通过DT之间的结构化合作，对生物标志物启用的临床试验进行概念验证研究 项目成员和基于TACR的临床研究者团队。通过将临床研究者纳入 在IND前阶段设计临床前研究，DT计划旨在简化临床药物 同时提高临床成功的可能性。 1英寸 "

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" "