Molecular Therapeutics (MT)

项目摘要/摘要：分子治疗学（MT） 分子治疗（MT）计划的目标是确定治疗靶点，药物和策略， 并促进达特茅斯研究者假设转化为临床试验。研究兴趣 该计划的教师涵盖了在分子治疗研究的全方位，包括合成 新的化合物作为研究工具和潜在的治疗;研究新的治疗靶点; 评估疾病进展或药物反应的预测因素;以及概念验证和早期治疗 阶段临床试验。MT计划目前有来自9个不同部门的30名成员，他们的研究 焦点可以用以下四个科学主题来描述：（1）新颖的合成和发现 化合物和潜在的癌症药物，（2）潜在的新靶点和治疗策略的询问，（3） 开发用于癌症诊断和预测治疗反应的生物标志物，和（4）开发用于癌症诊断和预测治疗反应的生物标志物。 基于假设的癌症临床试验。这四个研究主题并不是作为单独的实体存在的。有 它们之间广泛的相互作用，因为新的药物和化合物被用于询问新的靶点， 新的生物标志物正在被确定，这些进展正在被转化为分子证据， 主要临床试验。在这个范围内的相互作用是由相互作用的环境催化的 通过MT计划的活动产生，其在早期临床肿瘤学试验中的深度参与 集团（EPTCOG），并通过不断培养和指导计划成员的计划合作， 董事们。这项工作导致了整个分子治疗领域的广泛合作， 联合赠款和出版物就是证明。该计划对NCCC使命的主要贡献有 达特茅斯的翻译促进了新的治疗方法的发现， 临床试验中的研究者假设，以及此类研究的患者累积。此外，NCCC还 作出了实质性的承诺，以提高深度和广度的研究和临床翻译的MT 通过共享资源的支持，在财政上支持与早期- 阶段/原理验证临床试验，以及新研究者的战略招募。例如，在 在过去的5年里，该计划的成员随着成功招募优秀的新成员而不断发展。 生物实验室科学（米勒，黑川），化学（Micalizio，吴），以及 临床/转化研究（达尼洛夫、Lansigan、Smith）。超过363篇癌症相关文章 在本报告所述期间发表的论文（54篇[15%]在高影响力期刊上发表），其中许多代表了 计划（69=19%）或计划间（107=29%）合作。这些合作涉及29个MT项目 成员和63 NCCC成员，几乎平均分布在其他5个NCCC研究计划。 该计划目前的总资金为800万美元，其中600万美元是同行评审的，340万美元来自NCI。

Project Summary/Abstract: Molecular Therapeutics (MT) The goal of the Molecular Therapeutics (MT) Program is to identify therapeutic targets, drugs, and strategies, and to facilitate the translation of Dartmouth-investigator hypotheses into clinical trials. The research interests of the program faculty cover the full spectrum of investigations in molecular therapeutics and include synthesis of novel compounds as research tools and potential therapeutics; investigation of novel targets for therapy; assessment of predictors of disease progression or drug response; and proof-of-concept and therapeutic early phase clinical trials. The MT program currently has 30 members from 9 different departments whose research foci can be described under the following four scientific themes: (1) Synthesis and discovery of novel compounds and potential cancer drugs, (2) Interrogation of potential new targets and therapeutic strategies, (3) Development of biomarkers for cancer diagnosis and prediction of treatment response, and (4) Development of hypothesis-based cancer clinical trials. These four research themes do not exist as separate entities. There is extensive interaction between them, as novel drugs and compounds are used to interrogate novel targets, novel biomarkers are being identified, and these advances are being translated into molecular proof-of- principle clinical trials. The interactions across this spectrum are catalyzed by the interactive environment generated by activities of the MT program, its deep involvement in the Early Phase Trials Clinical Oncology Group (EPTCOG), and by the continual nurturing and mentoring of program members by the Program Co- Directors. This work results in extensive collaborations across the entire spectrum of molecular therapeutics, as evidenced by joint grants and publications. Major contributions of the program to the NCCC mission have been the facilitation of discoveries promising new therapeutic approaches, the translation of Dartmouth investigator hypotheses into clinical trials, and the accrual of patients to such studies. In addition, NCCC has made substantial commitment to improving the depth and breadth of research and clinical translation in the MT program through support of shared resources, financially supporting many of the costs associated with early- phase/proof-of-principle clinical trials, and strategic recruitment of new investigators. For example, over the past 5 years, the membership of the program has evolved with the successful recruitment of outstanding new faculty in the biological laboratory sciences (Miller, Kurokawa), chemistry (Micalizio, Wu), and in clinical/translational investigations (Danilov, Lansigan, Smith). More than 363 cancer-related articles have been published over the reporting period (54 [15%] in high impact journals), many of them representing intra- program (69=19%) or inter-program (107=29%) collaboration. These collaborations involve 29 MT program members and 63 NCCC members, almost equally distributed between the other 5 NCCC research programs. Total funding for the program currently is $8.0M, of which $6.0M is peer-reviewed and $3.4M is from NCI.