INTEGRATED ASSESSMENT OF NOVEL THERAPIES IN ONCOLOGY

肿瘤学新疗法的综合评估

• 批准号: 6522286
• 负责人: MACE L ROTHENBERG
• 金额: $ 11.17万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522286
• 关键词: antineoplastics; apoptosis; clinical research; clinical trials; combination chemotherapy; data collection methodology /evaluation; data management; drug resistance; enzyme activity; enzyme inhibitors; health science research support; human subject; human therapy evaluation; meeting /conference /symposium; metalloendopeptidases; neoplasm /cancer chemotherapy; neoplastic cell; prostaglandin endoperoxide synthase; role model; toxicology; training

The purpose of this K-24 grant proposal is to provide the support necessary for the principal investigator to conduct and to mentor trainees in the conduct of patient-oriented clinical research that bridges early phase clinical trials of novel cancer therapies with laboratory correlative studies. Trainees will be supervised in their clinical research by the principal investigator and in their laboratory research by a basic scientist skilled in that area. Research projects pursued under this grant will involve the development and use of laboratory models to guide clinical trial design and the establishment of laboratory assays to measure the impact of the therapeutic intervention on tissue and plasma samples collected during the course of the clinical trial. Two examples are provided. One involves measurement of the change in matrix metalloproteinase level and activity in tumor tissue obtained from a cohort of patients treated with a novel matrix metalloproteinase inhibitor. The other involves the development of in vitro and in vivo models leading to the clinical evaluation of the combination of cytotoxic chemotherapy and cyclooxygenase-2 inhibitors on established cancers. This hypothesis is based on 3 main observations: 1) COX-2 overexpression has an inhibitory effect on apoptosis; 2) most cytoxic agents exert their antitumor effect through apoptosis; and 3) many drug-resistant tumors, including more than 70 percent of adenocarcinomas of the colon and lung,overexpress COX-2. The principal investigator has been continuously involved in patient-oriented clinical research in a variety of capacities for 13 years. His work has focused primarily on new drug development in oncology and he has been extensively involved in the design and conduct of the clinical trials that led to the FDA approval of gemcitabine (for pancreatic cancer) and irinotecan (CPT-11) (for colorectal cancer). He currently directs the Phase I Drug Development Program at the Vanderbilt Cancer Center. This grant will permit the candidate to extend his experience to work more closely with basic researchers and clinical trainees in the development of integrated laboratory/clinical trials that can provide the greatest amount of information regarding the activity of novel cancer therapeutic agents.

这项 K-24 拨款提案的目的是为主要研究者提供必要的支持，以开展并指导学员进行以患者为导向的临床研究，将新型癌症疗法的早期临床试验与实验室相关研究联系起来。 受训者的临床研究将受到首席研究员的监督，实验室研究将受到该领域熟练基础科学家的监督。 这笔赠款下开展的研究项目将涉及开发和使用实验室模型来指导临床试验设计，以及建立实验室测定法来衡量治疗干预对临床试验过程中收集的组织和血浆样本的影响。 提供了两个示例。 其中一项涉及测量从接受新型基质金属蛋白酶抑制剂治疗的一组患者获得的肿瘤组织中基质金属蛋白酶水平和活性的变化。另一个涉及体外和体内模型的开发，从而对细胞毒性化疗和环氧合酶 2 抑制剂的组合对已确定的癌症进行临床评估。 这一假设基于3个主要观察结果：1）COX-2过表达对细胞凋亡有抑制作用； 2）大多数细胞毒药物通过细胞凋亡发挥抗肿瘤作用； 3)许多耐药肿瘤，包括70%以上的结肠癌和肺癌，过度表达COX-2。 13 年来，首席研究员一直以各种身份持续参与以患者为中心的临床研究。 他的工作主要集中于肿瘤学新药开发，并广泛参与了临床试验的设计和实施，这些试验使吉西他滨（用于胰腺癌）和伊立替康（CPT-11）（用于结直肠癌）获得 FDA 批准。 他目前负责范德比尔特癌症中心的一期药物开发项目。 这笔赠款将使候选人能够扩展其经验，以便与基础研究人员和临床实习生更密切地合作，开发综合实验室/临床试验，从而提供有关新型癌症治疗剂活性的最大量信息。