Delineate the Role of GSTP1 in Advanced Prostate Cancer

描述 GSTP1 在晚期前列腺癌中的作用

基本信息

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
项目类别：
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

项目摘要

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，迫切需要定义推动侵略性疾病并制定克服高级策略的机制耐药前列腺癌。我们最近表明，GSTP1蛋白在耐治疗的前列腺癌中显着上调。我们有强有力的初步证据表明，GSTP1可能在推动积极进取方面发挥功能作用前列腺癌，可能是晚期疾病的有前途的治疗靶标。我们最近有证明GSTP1在耐激素治疗的前列腺癌中显着升高，并且 GSTP1的抑制会抑制前列腺癌的生长。拟议项目的主要目标是： 1）测试GSTP1在晚期前列腺癌中的功能作用。 2）单独测试GSTP1抑制的治疗潜力，并与顺铂结合在侵略性使用患者衍生的异种移植物（PDX）模型的前临床环境中的前列腺癌。 3）描述GSTP1在晚期前列腺癌中的作用机理。成功完成拟议的研究将导致：1）定义GSTP1在侵略性治疗中的作用 - 耐药性前列腺癌和2）有关新型治疗干预措施的直接新策略疾病的致命形式。