COMBINATION THERAPY WITH BIOCHEMICAL MODULATION AND MCA

目的是实现有效的癌症联合化疗， 通过适当代谢调节相关酶途径 根据现有的代谢物-抗代谢物组合选择 生物化学知识和从拟议的生物化学研究中产生的知识。 正常和相对无害的化合物将被使用， 选择性地增强已知试剂的抗肿瘤效力（例如，胸苷， 5-氟尿嘧啶），或保护正常组织免受毒性（例如，睾酮 和/或尿苷与5-FU）。 方法是逐步的。 首先，代理商 在生物化学原理的基础上选择， 抗癌活性的潜在增益。 如果这伴随着不幸的 毒性，下一步是添加剂或正常代谢物， 选择性地保护宿主。 此过程继续添加 另一种药物产生进一步增强的肿瘤毒性，等等。这 这种方法的独特之处在于，控制严重的宿主毒性被认为是 对于实现化疗治愈至关重要，因为由此产生的 药物选择性的操作增加将允许定量和 化疗药物组合的质量增加。 的有效性 这种方法已被以前的工作所证实。

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.