Elucidating the Role of UCHL1 in Aggressive Prostate Cancer

阐明 UCHL1 在侵袭性前列腺癌中的作用

• 批准号: 10756690
• 负责人: Tanya I Stoyanova
• 金额: $ 21万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10756690
• 关键词: Elucidating; Role; UCHL1; Aggressive; Prostate

PROJECT SUMMARY/ABSTRACT Prostate cancer is the second leading cause of cancer associated deaths in men in the United States. The first line of treatment for men with advanced metastatic prostate cancer is hormone therapy. Although initial responses are observed, unfortunately, the disease commonly recurs in its aggressive hormone therapy- resistant form, which is largely responsible for prostate cancer-specific mortality. Thus, there is an urgent need to define the mechanisms that drive the aggressive disease. We have recently shown that UCHL1 protein is implicated in regulating aggressive prostate cancer growth and prostate cancer metastasis. We have strong preliminary evidence suggesting that UCHL1 may be a new promising therapeutic target for aggressive prostate cancer. We have recently demonstrated that inhibition of UCHL1 suppresses prostate cancer growth. The main goals of the proposed project are: 1) test the functional role of UCHL1 in advanced prostate cancer. 2) investigate the molecular mechanism through which UCHL1 signals in aggressive prostate cancer. 3) test the therapeutic potential of UCHL1 inhibition in animal models of aggressive disease and patient-derived xenografts in preclinical settings. Successful completion of the proposed research will lead to: 1) defining the role of UCHL1 in aggressive therapy- resistant prostate cancer, 2) the discovery of new molecular mechanisms underlying UCHL1 function and the development of aggressive prostate cancer which will guide us towards novel therapeutic strategies to target the advanced disease and 3) direct new strategies regarding novel therapeutic interventions to combat the deadly form of the disease.

项目摘要/摘要 前列腺癌是美国男性癌症相关死亡的第二大原因。第一个 晚期前列腺癌男性的治疗线是激素治疗。虽然是最初的 不幸的是，观察到该疾病通常在其侵略性激素治疗中复发 - 抗性形式，主要负责前列腺癌特异性死亡率。因此，迫切需要 定义驱动侵略性疾病的机制。 我们最近表明，UCHL1蛋白与调节攻击性前列腺癌的生长和 前列腺癌转移。我们有大量的初步证据表明UCHL1可能是新的 侵略性前列腺癌的有希望的治疗靶标。我们最近证明了抑制 UCHL1抑制了前列腺癌的生长。 拟议项目的主要目标是： 1）测试UCHL1在晚期前列腺癌中的功能作用。 2）研究UCHL1在侵袭性前列腺癌中信号的分子机制。 3）在侵略性疾病和患者衍生的动物模型中测试UCHL1抑制的治疗潜力 临床前环境中的异种移植物。 成功完成拟议的研究将导致：1）定义UCHL1在侵略性治疗中的作用 - 耐药性前列腺癌，2）发现UCHL1功能下的新分子机制和 开发侵略性前列腺癌，这将指导我们采取新颖的治疗策略以针对目标 晚期疾病和3）有关新型治疗干预措施的直接新策略，以对抗致命 疾病的形式。