MOLECULAR THERAPEUTICS RESEARCH PROGRAM

分子治疗研究计划

基本信息

批准号：
7944597
负责人：
ALAN R EASTMAN
金额：
$ 5.43万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-21 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7944597
关键词：
Apoptosis Apoptotic Area Basic Science Biological Monitoring Biopsy Cancer Center Cancer Center Support Grant Cancer Patient Cell Cycle Regulation Cisplatin Clinical Clinical Trials Collaborations Development Diagnosis Disease Disease Outcome Drug effect disorder Faculty Fatty-acid synthase Fostering Funding Goals Gossypium Investigation MCL1 protein Malignant neoplasm of pancreas Molecular Molecular Target Neoadjuvant Therapy New Agents Non-Small-Cell Lung Carcinoma Outcome Paper Pathway interactions Pharmaceutical Preparations Phase Phase I Clinical Trials Productivity Proteasome Inhibitor Proteins Publications Research Research Personnel Role Series Signal Transduction Testing Therapeutic Therapeutic Clinical Trial Therapeutic Human Experimentation Translating Translations Tumor Tissue cancer therapy clinical application drug discovery expectation improved inhibitor/antagonist malignant breast neoplasm member new technology novel novel strategies novel therapeutics programs smoothened signaling pathway treatment strategy tumor tumor growth tumor progression

项目摘要

The goal of the Molecular Therapeutics Program (MT) is to foster the exchange of ideas, cooperation, and collaboration leading to translation of basic research focused on the identification and development of novel therapeutics into clinical applications, and to use basic research to answer clinical questions related to improving the treatment of cancer. The MT Program provides a forum for discussion and advancement of new developments in target identification, drug discovery, and mechanisms of drug action, and for translating these approaches into novel correlative and therapeutic clinical trials. The Program currently has 27 members from 7 departments and $8.2 millon in total funding, of which almost $4 million (61%) is from the NCI. The productivity over the past 5 years exceeds 240 papers, including 16% intra-program and 26% interprogram collaborative publications. Eighteen Program faculty participated in intra-program and 18 in interprogram collaborations, providing strong evidence of a highly interactive research program. Recent programmatic highlights include evidence for the role of the fatty acid synthase pathway as an independent marker of breast cancer progression, and the recognition that it can be targeted to suppress tumor growth. Other molecular targets under investigation include proteins in the Hedgehog signaling pathway, which is frequently activated in non-small cell lung cancer. New agents such as novel proteasome inhibitors and suppressors of the anti-apoptotic proteins Mcl-1 and Bcl-2 are under investigation, with the expectation of bringing these drugs to clinical trial at Morris Cotton Cancer Center. Novel treatment strategies developed in the MT Program that have been translated into Phase I clinical trials include the combination of cisplatin plus the Chk1 inhibitor UCN-01. In is study serial tumor biopsies were used to monitor biological activity in tumor tissue. Other investigators have developed novel technologies and complementary approaches to define predictive markers and therapeutic strategies, and an important goal of the MT Program is to test these ideas in correlative and therapeutic clinical trials at the NCCC. Also worthy of particular notice is a series of Phase I and II clinical trials in pancreatic cancer using chemoradiation in the neoadjuvant setting that has identified a promising treatment approach in this highly aggressive disease and demonstrates the Program's impact on disease outcome in cancer patients.

分子治疗计划 (MT) 的目标是促进思想交流、合作和合作导致基础研究的转化，重点是小说的识别和开发疗法进入临床应用，并利用基础研究来回答相关的临床问题改善癌症的治疗。 MT 计划提供了一个讨论和推进的论坛靶标识别、药物发现、药物作用机制以及转化方面的新进展这些方法进入新颖的相关和治疗性临床试验。该计划目前有 27 成员来自 7 个部门，总资金 820 万美元，其中近 400 万美元（61%）来自国家癌症研究所。过去5年的论文产量超过240篇，其中项目内论文占16%，项目间论文占26% 合作出版物。 18 名项目教师参与项目内，18 名教师参与项目间合作，为高度互动的研究计划提供了有力的证据。最近的程序亮点包括脂肪酸合酶途径作为独立途径的作用的证据乳腺癌进展的标志物，并认识到它可以有针对性地抑制肿瘤生长。其他正在研究的分子靶点包括 Hedgehog 信号通路中的蛋白质，该通路是在非小细胞肺癌中经常被激活。新药物，例如新型蛋白酶体抑制剂和抗凋亡蛋白 Mcl-1 和 Bcl-2 的抑制因子正在研究中，预计将这些药物在莫里斯科顿癌症中心进行临床试验。开发的新治疗策略已转化为I期临床试验的MT计划包括顺铂+顺铂的联合治疗 Chk1 抑制剂 UCN-01。在这项研究中，使用连续肿瘤活检来监测肿瘤的生物活性组织。其他研究人员开发了新技术和补充方法来定义预测标记和治疗策略，MT 计划的一个重要目标是测试这些 NCCC 相关和治疗性临床试验的想法。另外值得特别关注的是一系列在新辅助治疗中使用放化疗治疗胰腺癌的 I 期和 II 期临床试验确定了一种治疗这种高度侵袭性疾病的有前途的治疗方法，并证明了该计划的对癌症患者疾病结果的影响。