Developmental Therapeutics Research Program

项目总结（见说明）： 发展治疗学（DT）研究计划是一个长期的研究计划，成立于1974年，是耶鲁大学癌症中心（YCC）的第一个研究计划。该方案有48名成员，代表15个部门。DT计划有三个主要目标：1。确定和表征用于治疗癌症和癌症相关病毒性疾病的关键分子靶点和治疗策略; 2.促进和促进对药物开发感兴趣的基础和临床研究者之间的互动; 3.将YCC的发现和科学转化为临床，使用临床试验探索预后，预测和药效学生物标志物。该计划在开发治疗方法方面非常成功，正如最近科学成就的快照所示。在上一个资助期内启动的工作中，DT成员发现了25种分子; 18种已被授权给制药行业; 9种正在进行临床前测试; 6种抗癌药物正在I、II和III期临床试验中进行临床测试。这包括2012年7月获得FDA批准的卡非佐米，该药物是在克雷格克鲁斯的实验室中开发的。DT计划的新领导人是Karen S。安德森博士和罗伊S. Herbst，医学博士，博士，在基于结构的药物设计/药物发现和转化研究，个性化癌症治疗和临床试验方面具有基础科学和临床/转化专业知识。安德森博士的主要作用是促进基础科学临床合作伙伴关系，并促进基础科学发现转化为临床前研究。Herbst博士的角色是促进翻译和临床项目。这包括建立由基础、临床和人口科学家组成的多研究者团队，作为肿瘤类型工作组，专注于各种类型的癌症。此外，我们聘请了Paul Eder博士领导第一阶段DT工作。在这一新的领导下，未来将有更多的分子进入耶鲁大学的试验。DT成员以癌症为重点的研究从YCC试点赠款资助中受益匪浅。自上次提交以来，YCC试点资金中的855，727美元已产生超过840万美元的校外资金，包括1个ROI和1个P01以及2个临床试验。DT计划的资金相当强劲，与癌症相关的资金总额为16，693，963美元。其中，超过80%是同行评审的（13，233，968美元），4，240，718美元（2.8美元的直接成本）来自NCI。在上一个资助期（2006-11年），该项目的成员发表了397篇与癌症相关的论文。这包括179个合作项目，其中42%是方案间项目，9%是方案内项目。

PROJECT SUMMARY (See instructions): The Developmental Therapeutics (DT) Research Program is a long-standing research program, established in 1974 as the first research program of the Yale Cancer Center (YCC). This program has 48 members representing 15 departments. The DT program has three main program goals: 1. To identify and characterize key molecular targets and therapeutic strategies for treatment of cancer and cancer-associated viral disease; 2. To foster and facilitate interactions between basic and clinical investigators interested in drug development; and 3. To translate YCC discoveries and science into the clinic using clinical trials which explore prognostic, predictive and pharmacodynamic biomarkers. This program has been highly successful in developing therapeutics as illustrated by considering a snapshot of recent scientific accomplishments. In work initiated during the previous grant period, twenty-five molecules have been discovered by DT members; 18 have been licensed to the pharmaceutical industry; 9 are undergoing preclinical testing; and 6 anticancer agents are in clinical testing in Phase I, II, and III trials. This includes carfilzomib that received FDA approval in July 2012 that was developed in the lab of Craig Crews in the previous grant period. The new leaders of the DT Program are Karen S. Anderson, PhD and Roy S. Herbst, MD, PhD, with basic science and clinical/translational expertise in structure-based drug design/drug discovery and translational research, personalized cancer therapies, and clinical trials. Dr. Anderson's primary role is to foster basic science clinical partnerships and facilitate the translation of basic science discoveries to preclinical studies. Dr. Herbst's role is to promote translational and clinical programs. This includes building multi-investigator teams comprised of basic, clinical, and population scientists assembled as tumor-type working groups that are focused on the various types of cancer. In addition, we recruited Dr. Paul Eder to lead the Phase I, DT effort. Under this new leadership, more molecules will enter trials at Yale in the future. The cancer-focused research of DT members has significantly benefited from YCC pilot grant funding. Since the last submission, $855,727 in YCC pilot funds have yielded over $8.4 million in extramural funding including 1 ROI and 1 P01 as well as 2 clinical trials. The funding in the DT program is quite robust with a total cancer-related funding of $16,693,963. Of this, over 80% is peer-reviewed ($13,233,968) and $4,240,718 ($2.8 direct costs) is from NCI. During the previous grant period (2006-11), members of this program published 397 cancer-related papers. This includes 179 that were collaborative, of which 42% were inter-programmatic and 9% were intraprogrammatic.