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/文摘