ENERGY BALANCE IN PROSTATE CANCER

前列腺癌占12.2万新病例和3万与癌症相关的病例 美国每年的死亡人数。尽管荷尔蒙疗法 对大约70%的转移性癌症患者有效， 最终，他们都会患上雄激素非依赖性进行性疾病。 前列腺癌。目前还没有有效的雄激素非依赖性治疗方法 前列腺癌。 抗寄生虫药物苏拉明在人体内具有抗增殖作用 癌细胞。最近，苏拉明在 前列腺癌患者。我们已经找到了证据证明 迅速抑制细胞呼吸，扰乱细胞能量 完整的前列腺癌细胞的平衡。能量平衡被破坏或 呼吸是癌症中一种可能的抗增殖机制 细胞，被认为是苏拉明作用的主要机制 寄生虫病。这种苏拉明的作用机制可以 解释观察到的最显著的临床毒性 肾毒性、肾上腺毒性、凝血障碍和脱髓鞘 神经病。 这份提案概述了我们使用苏拉明作为靶向目标的模型的计划 抗肿瘤治疗中的细胞能量代谢。我们已经概述了一个 进一步阐明苏拉明作用机制的实验计划 利用这一知识寻找与苏拉明有协同作用的其他药物。 最后，我们计划利用我们的第一阶段药物开发计划来应用 临床环境中的这一知识，从我们正在进行的第一阶段开始 苏拉明试验。

Prostate cancer accounts for 122,000 new cases and 30,000 cancer-related deaths in the United States each year. Although hormone therapy is effective in approximately 70% of the men with metastatic cancer, ultimately they all suffer progressive disease with androgen-independent prostate cancer. No effective therapy exists for androgen-independent prostate cancer. The antiparasitic drug, suramin, has antiproliferative effects in human carcinoma cells. Most recently, suramin has demonstrated activity in patients with prostate cancer. We have developed evidence that suramin rapidly inhibits cellular respiration and disrupts cellular energy balance in intact prostate cancer cells. Disruption of energy balance or respiration represents a possible antiproliferative mechanism in cancer cells, as is felt to be a primary mechanism for suramin's action in parasitic diseases. This proposed mechanism of action for suramin can explain the most prominently observed clinical toxicities of nephrotoxicity, adrenal toxicity, coagulopathy and demyelinating neuropathy. This proposal outlines our plan to use suramin as a model to target cellular energy metabolism in antineoplastic therapy. we have outlined an experimental plan to further delineate suramin's mechanism of action and use of this knowledge to search for other drugs synergistic to suramin. Finally, we plan to utilize our Phase I drug development program to apply this knowledge in clinical settings, starting with our ongoing Phase I trial of suramin.