Delineate the Role of GSTP1 in Advanced Prostate Cancer

描述 GSTP1 在晚期前列腺癌中的作用

• 批准号: 10607918
• 负责人: Tanya I Stoyanova
• 金额: $ 46.73万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-14 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10607918
• 关键词: Advanced Development; Aggressive Clinical Course; Androgens; Automobile Driving; Binding; Cancer Etiology; Castration; Cells; Cessation of life; Cisplatin; Combined Modality Therapy; Development; Disease; Down-Regulation; Drug Metabolic Detoxication; Enzymes; Epithelial Cells; FDA approved; Family; Future; GSTP1 gene; Glutathione S-Transferase; Glycolysis; Goals; Growth; Human; Incidence; Life Expectancy; Malignant neoplasm of prostate; Metastatic Prostate Cancer; Modeling; Molecular; Neoplasm Metastasis; Neurosecretory Systems; Pathway interactions; Patients; Phenotype; Play; Prostate; Proteins; Proteomics; Proto-Oncogene Proteins c-akt; Recurrence; Relapse; Research; Resistance; Role; Signal Transduction; Testing; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Time; Tissues; United States; advanced disease; advanced prostate cancer; aggressive therapy; androgen deprivation therapy; castration resistant prostate cancer; clinically relevant; cohort; combat; hormone therapy; inhibitor; insight; member; men; mortality; neuroendocrine phenotype; new combination therapies; novel; novel strategies; novel therapeutic intervention; overexpression; patient derived xenograft model; pre-clinical; preclinical study; prostate cancer metastasis; response; standard of care; therapeutic candidate; therapeutic evaluation; therapeutic target; therapy resistant; tumor; tumor growth; tumor xenograft

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 and develop novel strategies to overcome advanced treatment-resistant prostate cancer. We have recently shown that GSTP1 protein is significantly upregulated in treatment-resistant prostate cancer. We have strong preliminary evidence suggesting that GSTP1 may play functional role in driving aggressive prostate cancer and may represent a promising therapeutic target for the advanced disease. We have recently demonstrated that GSTP1 is significantly elevated in hormone therapy-resistant prostate cancer and that inhibition of GSTP1 suppresses prostate cancer growth. The main goals of the proposed project are: 1) test the functional role of GSTP1 in advanced prostate cancer. 2) test the therapeutic potential of GSTP1 inhibition alone and in combination with cisplatin in aggressive prostate cancer in pre-clinical settings utilizing patient-derived xenograft (PDX) models of NEPC. 3) Delineate the mechanism of action of GSTP1 in advanced prostate cancer. Successful completion of the proposed research will lead to: 1) defining the role of GSTP1 in aggressive therapy- resistant prostate cancer and 2) direct new strategies regarding novel therapeutic interventions to combat the deadly form of the disease.

项目总结/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 晚期转移性前列腺癌的治疗线是激素疗法。尽管最初 不幸的是，这种疾病通常在其积极的激素治疗中复发- 耐药形式，这在很大程度上负责前列腺癌特异性死亡率。因此，迫切需要 确定驱动侵袭性疾病的机制，并开发新的策略来克服晚期 难治性前列腺癌 我们最近发现，GST P1蛋白在治疗抵抗性前列腺癌中显著上调。 我们有强有力的初步证据表明，GSTP 1可能在驱动攻击性行为中发挥功能性作用， 前列腺癌和可能代表一个有前途的治疗目标的先进的疾病。我们最近 证明GSTP 1在激素治疗抵抗性前列腺癌中显著升高， 抑制GSTP 1可抑制前列腺癌生长。 拟议项目的主要目标是： 1)测试GST P1在晚期前列腺癌中的功能作用。 2)测试GSTP 1单独抑制和与顺铂组合在侵袭性肿瘤中的治疗潜力。 在临床前环境中使用NEPC的患者来源的异种移植物（PDX）模型的前列腺癌。 3)GSTP 1在晚期前列腺癌中的作用机制 成功完成拟议的研究将导致：1）确定GST 1在积极治疗中的作用- 耐药前列腺癌和2）关于新的治疗干预的新策略，以对抗 这种疾病的致命形式。