COMBINATION THERAPY WITH BIOCHEMICAL MODULATION AND MCA

其目标是实现癌症的有效联合化疗和 适当调节相关酶途径的代谢 代谢物-抗代谢物组合基于现有的 生物化学知识和从拟议的生物化学研究中产生的知识。 通常和相对无害的化合物将被用来 选择性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，睾酮 和/或尿苷加5-FU)。这种方法是循序渐进的。首先，代理 根据生化原理选择的是在体内结合的 在抗癌活性方面的潜在收益。如果这伴随着不愉快 毒性，下一步是添加一种试剂或正常的代谢物 有选择地保护宿主。此过程继续进行，添加了 另一种药物产生的肿瘤毒性进一步增强，等等。这 方法是独特的，因为控制严重的寄主毒性被认为是 对于实现化疗治愈是必不可少的，因为由此产生的 操作上药物选择性的增加将允许数量和 化疗药物组合的质量增加。法律的有效性 这一方法得到了以前的工作的证实。

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.