COMBINATION THERAPY WITH BIOCHEMICAL MODULATION AND MCA

生化调节和 MCA 联合治疗

• 批准号: 3093111
• 负责人: DANIEL S MARTIN
• 金额: $ 99.23万
• 依托单位: CATHOLIC MEDICAL CTR OF BKLYN & QUEENS
• 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 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3093111
• 关键词: combination cancer therapy; drug metabolism; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy

The objective is to achieve effective combination chemotherapy of cancer with the aid of metabolic modulation of relevant enzymatic pathways by appropriate metabolite-antimetabolite combinations selected on the basis of both existing biochemical knowledge and that generated from the proposed biochemical studies. Normal and comparatively innocuous compounds will be employed either to selectively enhance the antitumor potency of known agents (e.g., thymidine with 5-fluorouracil), or to protect normal tissue from toxicity (e.g., testosterone and/or uridine with 5-FU). The methodology is step-wise. First, agents selected on the basis of a biochemical rationale are combined in vivo for potential gain in anti-cancer activity. If this is accompanied by untoward toxicity, the next step is the addition of an agent or normal metabolite to selectively protect the host. This procedure continues with the addition of another drug to yield further augmentation of tumor toxicity, and so on. This approach is unique in that the control of serious host toxicity is considered to be essential to the achievement of chemotherapeutic cure, because the resulting operational increase in drug selectivity will allow both a quantitative and a qualitative increase in the chemotherapeutic drug combination. The validity of this approach is substantiated by previous work.

目的是与 通过适当的 基于现有的 生化知识以及拟议的生化研究产生的知识。 正常和相对无害的化合物将使用 有选择地增强已知药物的抗肿瘤效力（例如，胸苷与 5-氟尿嘧啶），或保护正常组织免受毒性（例如睾丸激素 和/或5-FU）。 该方法是逐步的。 首先，代理商 根据生化原理选择的体内合并 抗癌活性的潜在增益。 如果伴随着不愉快的 毒性，下一步是将代理或正常代谢物添加到 有选择地保护主机。 此过程继续添加 另一种导致肿瘤毒性进一步增强的药物，依此类推。 这 方法是独一无二的，因为对严重的宿主毒性的控制被认为 对于实现化学治疗至关重要，因为由此产生 药物选择性的运营提高将允许定量和 化学治疗药物组合的质量增加。 的有效性 以前的工作证实了这种方法。