ENERGY BALANCE IN PROSTATE CANCER

前列腺癌占122，000例新病例和30，000例癌症相关病例 美国每年的死亡人数。 虽然激素治疗是 对大约70%的转移性癌症患者有效， 最终他们都患有进行性疾病， 前列腺癌 对于雄激素非依赖性 前列腺癌 抗寄生虫药苏拉明在人体内具有抗增殖作用， 癌细胞 最近，苏拉明已被证明在 前列腺癌患者。 我们有证据表明苏拉明 迅速抑制细胞呼吸并破坏细胞能量 在完整的前列腺癌细胞中保持平衡。 破坏能量平衡或 呼吸是癌症中一种可能的抗增殖机制 细胞，因为被认为是苏拉明的行动， 寄生虫病 苏拉明的这种作用机制可以 解释了最显著的临床毒性 肾毒性、肾上腺毒性、凝血病和脱髓鞘 神经病变 该提案概述了我们的计划，以苏拉明为模型， 细胞能量代谢的影响。我们概述了一个 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协同作用的其他药物。 最后，我们计划利用我们的I期药物开发计划， 从我们正在进行的第一阶段开始， 苏拉明的审判

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.