Experimental and Developmental Therapeutics Program

摘要、实验和发展治疗计划(EDT) EDT计划的使命是促进、开发和利用基于机制的研究，以改进 人类癌症的治疗。EDT的目标是：1)阐明新的癌症选择靶点 开发抗肿瘤药物；2)开发针对癌症的新型抗肿瘤药物 靶点；以及3)开展癌症选择性抗肿瘤靶点的临床前和临床研究 新的生物标志物。为了实现这一点，EDT计划提供了一个有组织的、基于科学的渠道 将IUSCC的发现从实验室转化为临床，并帮助建立适当的临床前 便于临床翻译的模型和数据。同样，临床数据产生了新的假设，由 在整个IUSCC具有坚实的基础科学基础。EDT的节目主题侧重于识别 新的癌症选择途径，随后是药物和生物标记物的发现，以确定最佳人群 从我们的基础科学实验室产生的新疗法。EDT计划有两个主题： 主题1：新的癌症选择靶点和抗肿瘤药物用于治疗开发；和 2：以机制为基础的研究试验。临床前主题1下的目标是：1)研究DNA的作用 修复，遗传不稳定和维持；以及2)阐明细胞信号级联反应的靶点和 新陈代谢。在临床翻译主题2下有两个目标：1)翻译临床前研究 表观遗传学和选择性抗肿瘤药物的研究；以及2)进行基于机制的临床试验。美国东部夏令时 该计划有两位高度成就和互补的联合领导人，Boothman博士和Pili博士，他们领导着46 印第安纳大学梅尔文和布伦·西蒙癌症中心(IUSCC)成员(35名正式成员和11名准成员)， 包括来自15个部门的32名基础科学研究人员和14名临床研究人员，以开发新的 并通过开展研究人员发起的临床试验来评估这些方法。这个 该项目共有810万美元的同行评议资金，其中600万美元来自NCI，130万美元来自其他NIH 研究所。EDT计划显示NCI资金增加了3倍以上，从190万美元增加到600万美元(直接 在上一次授权期内)。通过这项计划，2615名患者参加了治疗试验 2013-17年(平均每年超过500人)，其中63%来自研究所、国家合作社或外部 同行评议的研究，只有36%来自行业赞助的试验。经过同行评审的平均资金 在过去的资助期内，每个正式会员从16.8万美元增加到23.2万美元。计划成员是 高度协作，29%的方案间、20%的方案内和63%的方案间 机构出版物。EDT计划成员还发表了429篇出版物，其中81篇(19%)在High 影响日志。这一高度互动的计划与其他计划建立了牢固的合作伙伴关系 (HHM、TMM和CPC)，并从通过招募、教育和教育等方式支持国际自然保护联盟委员会中受益匪浅 此外，教科文组织还将在场地、试点项目，如“近身小姐”倡议及其共享资源的开发方面开展合作。

ABSTRACT, Experimental and Developmental Therapeutics Program (EDT) The mission of the EDT Program is to promote, develop, and exploit mechanism-based research for improved therapy of human cancer. The objectives of EDT are: 1) To elucidate novel cancer-selective targets for development of antitumor agents; 2) To develop novel antitumor agents that are specifically directed at cancer targets; and 3) To develop preclinical and clinical studies of cancer-selective antitumor targets with associated novel biomarkers. To accomplish this, the EDT Program provides an organized, science-based conduit for translating IUSCC discoveries from the laboratory to the clinic, and to help establish appropriate preclinical models and data to facilitate clinical translation. Likewise, clinical data generate new hypotheses tested by the strong basic science foundation throughout the IUSCC. The Program themes of EDT focus on identification of novel cancer-selective pathways followed by drug and biomarker discovery to identify optimal populations for the new treatments that emanate from our basic science laboratories. The EDT Program has two themes: Theme 1: Novel cancer-selective targets and antitumor agents towards therapeutic development; and Theme 2: Mechanism-based research trials. The aims under the preclinical Theme 1 are: 1) To investigate roles of DNA repair, genetic instability and maintenance; and 2) To elucidate targets in cell signaling cascades and metabolism. Under the clinical translational Theme 2 are two aims: 1) To translate preclinical studies of epigenetics and of selective antitumor agents; and 2) To conduct mechanism-based clinical trials. The EDT Program has two highly accomplished and complementary Co-Leaders, Drs. Boothman and Pili, who lead 46 Indiana University Melvin and Bren Simon Cancer Center (IUSCC) members (35 Full and 11 Associate), including 32 basic science investigators and 14 clinical investigators from 15 Departments, to develop novel therapeutic strategies and to evaluate these approaches by conducting investigator-initiated clinical trials. The Program has a total of $8.1M in peer-reviewed funding, with $6M from the NCI and $1.3M from other NIH Institutes. The EDT Program demonstrated over a 3-fold increase in NCI-funding from $1.9M to $6M (Direct Costs) during the last grant period. Through this Program, 2,615 patients have been entered on therapeutic trials from 2013-17 (average over 500/year) of which 63% were from IITs, National Cooperative Group or external peer-reviewed studies and only 36% were from industry-sponsored trials. The average peer-reviewed funding per Full Member has increased from $168K to $232K during the past funding period. Program members were highly collaborative as highlighted by 29% Inter-programmatic, 20% intra-programmatic and 63% inter- institutional publications. EDT Program members also contributed to 429 publications, including 81 (19%) in high impact journals. This highly interactive Program has established strong partnerships with the other Programs (HHM, TMM and CPC) and has benefited greatly from support of the IUSCC through recruitment, educational venues, pilot projects such as the “Near-Miss” Initiative and development of its Shared Resources.