Experimental and Developmental Therapeutics Program

实验和发展治疗学项目（EDT） EDT计划的使命是促进、发展和利用基于机制的研究， 人类癌症的治疗。EDT的目标是：1）阐明新的癌症选择性靶点， 开发抗肿瘤药物; 2）开发特异性针对癌症的新型抗肿瘤药物 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。为了实现这一目标，EDT计划提供了一个有组织的，以科学为基础的渠道， 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 模型和数据，以促进临床翻译。同样，临床数据产生了新的假设， 整个IUSCC的强大基础科学基础。EDT的计划主题侧重于识别 新的癌症选择性途径，随后是药物和生物标志物的发现，以确定最佳人群， 基础科学实验室的新疗法。EDT计划有两个主题： 主题1：新的癌症选择性靶点和抗肿瘤药物的治疗开发; 2：基于机制的研究试验。临床前主题1的目的是：1）研究DNA的作用 修复、遗传不稳定性和维持;以及2）阐明细胞信号级联中的靶点， 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;和2）进行基于机制的临床试验。该能量检测 该计划有两个高度成就和互补的共同领导人，博士Boothman和皮利，谁领导46 印第安纳州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名副成员）， 包括来自15个部门的32名基础科学研究者和14名临床研究者， 治疗策略，并通过进行药物启动的临床试验来评估这些方法。的 该计划共有810万美元的同行评审资金，其中600万美元来自NCI，130万美元来自其他NIH 院所EDT计划表明，NCI资金从190万美元增加到600万美元（直接 在最后一个补助期内。通过这一方案，2，615名患者参加了治疗试验 从2013年到2017年（平均每年超过500人），其中63%来自IIT、国家合作组或外部 同行评议的研究，只有36%来自行业赞助的试验。平均同行评审资金 在过去的资助期间，每位正式成员的资金从168 K美元增加到232 K美元。项目成员为 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计划成员还为429篇出版物做出了贡献，其中81篇（19%）在高 影响期刊。这个高度互动的项目与其他项目建立了强有力的合作伙伴关系 (HHM，TMM和CPC），并通过招聘，教育和培训， 该中心还将继续努力，在一些场地、“未遂事件”倡议等试点项目以及开发其共享资源方面开展工作。

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.