Molecular Therapeutics (MT)

项目摘要/摘要：分子治疗(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人员假设转化为临床试验。研究兴趣 该项目的教职员工涵盖了分子治疗学的所有研究领域，包括合成 将新化合物作为研究工具和潜在的治疗方法；调查新的治疗靶点； 评估疾病进展或药物反应的预测因素；以及概念验证和治疗早期 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 焦点可以在以下四个科学主题下描述：(1)小说的合成和发现 化合物和潜在的抗癌药物，(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治疗反应预测的生物标志物，以及(4)开发 基于假设的癌症临床试验。这四个研究主题不是作为单独的实体存在的。的确有 它们之间的广泛相互作用，因为新的药物和化合物被用来审问新的目标， 新的生物标志物正在被识别，这些进展正在转化为分子证据- 原则性临床试验。整个光谱的相互作用是由交互环境催化的 由MT计划的活动产生，其深度参与临床肿瘤学的早期试验 集团(EPTCOG)，以及计划合作伙伴对计划成员的持续培养和指导 董事们。这项工作导致了在整个分子治疗学领域的广泛合作， 联合赠款和出版物证明了这一点。该计划对NCCC任务的主要贡献有 促进了有希望的新治疗方法的发现，达特茅斯的翻译 研究人员对临床试验的假设，以及患者对此类研究的收益。此外，NCCC还拥有 致力于提高MT研究和临床翻译的深度和广度 计划通过支持共享资源，在财务上支持与早期- 阶段/原则验证临床试验，以及战略性招募新的研究人员。例如，在 在过去的5年里，该计划的成员资格随着优秀新员工的成功招聘而不断发展 生物实验科学(Miller，Kurokawa)、化学(Micalizio，Wu)和 临床/转换研究(Danilov、Lansigan、Smith)。超过363篇与癌症相关的文章 在本报告所述期间发表(54[15%]在高影响力期刊上)，其中许多代表内部 计划(69=19%)或计划间协作(107=29%)。这些协作涉及29个MT计划 成员和63名NCCC成员，几乎平均分布在其他5个NCCC研究项目中。 该项目目前的总资金为800万美元，其中600万美元来自同行审查，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.