COMBINATION THERAPY WITH BIOCHEMICAL MODULATION AND MCA

生化调节和 MCA 联合治疗

• 批准号: 3093113
• 负责人: DANIEL S MARTIN
• 金额: $ 107.54万
• 依托单位: ST. VINCENT CATHOLIC MEDICAL CTR NURSING
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3093113
• 关键词: combination cancer therapy; combination chemotherapy; drug metabolism; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy

The ultimate goal of the proposed research program is the development of both safer and more effective combination chemotherapy for cancer based on biochemical modulation. Drug combinations, or drug-metabolite combinations, selected on the basis of known or potential biochemical interaction will be utilized to manipulate relevant biochemical pathways in a therapeutically beneficial manner to either potentiate selective cytotoxicity in tumor cells, and/or to selectively diminish toxicity in normal host cells. In addition, a monoclonal antibody (MCA) to the epidermal growth factor receptor of the murine breast tumor, will be integrated into a combined treatment plan with the biochemically selected antimetabolite-metabolite combinations. The goal is to increase both the power and selectively of the therapeutic attack, hopefully to the level of cure of advanced, spontaneous solid cancers, first in a murine model and then ultimately in patients. This approach requires the integration of 4 projects: Project 1, Experimental Chemotherapy; Project 2, Biochemical Studies; Project 3, Monoclonal Antibody Studies; and Project 4, Clinical Studies. Preclinical chemotherapy studies (Project 1) will be performed entirely in in vivo murine tumor models. Therapeutic results from a particular drug manipulation, obtained as expected on the basis of the biochemical information that prompted that minipulation, will be confirmed on a biochemical level (Project 2) to insure that the biological results are related to the predicted biochemical changes. Unexpected therapeutic results will be explored at the biochemical level to provide new information that will be utilized to alter the drug combination (or schedule) so as to achieve the desired therapeutic advance. In vivo biochemical and pharmacological studies (Project 2) in the same animal tumor models will provide guidelines for comparative pharmacologic and biochemical studies in the clinic (project 4) which will be used to adjust promising therapeutic drug regimens for translation from the animal tumor model to cancer patients. The combined in vivo biological and biochemical findings, Projects 1, 2, lead to guidelines for specific clinical trials, and feedback from the clinical studies may suggest new experimental studies and refinements.

拟议研究计划的最终目标是 开发更安全，更有效的组合 基于生化调节的癌症化学疗法。 药品 在该组合中选择的组合或药物 - 代谢物组合 已知或潜在的生化相互作用的基础是 用于操纵相关的生化途径 在治疗上有益的方式来增强选择性 肿瘤细胞中的细胞毒性和/或选择性降低毒性 在正常宿主细胞中。 另外，单克隆抗体（MCA） 鼠乳腺肿瘤的表皮生长因子受体， 将与 生化选择的抗代谢物 - 代谢物组合。 目的是增加功率和选择性 治疗攻击，希望达到高级治疗水平， 自发固体癌症，首先是在鼠模型中，然后 最终在患者中。 这种方法需要4 项目：项目1，实验化疗；项目2， 生化研究；项目3，单克隆抗体研究；和 项目4，临床研究。 临床前化疗研究 （项目1）将完全在体内鼠肿瘤中进行 型号。 特定药物操纵的治疗结果， 根据生化信息如预期获得的 这促使大会将在 生化水平（项目2）确保生物学结果 与预测的生化变化有关。 意外 治疗结果将在生化水平探讨 提供将用于更改药物的新信息 组合（或时间表）以实现所需的治疗 进步。 体内生化和药理学研究 （项目2）在同一动物肿瘤模型中将提供 比较药理学和生化研究指南 在诊所（项目4）中，该诊所将用于调整有希望的 从动物肿瘤翻译的治疗药物方案 癌症患者的模型。 体内生物学和 生化发现，项目1，2，导致特定指南 临床试验和临床研究的反馈可能表明 新的实验研究和改进。