In Vivo Efficacy of Multi-Targeted Androgen Inhibition as Prostate Cancer Therapy

多靶点雄激素抑制作为前列腺癌治疗的体内疗效

基本信息

批准号：
7472502
负责人：
ELAHE A MOSTAGHEL
金额：
$ 13.45万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-15 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7472502
关键词：
Accounting Achievement Address Adrenal Glands Agonist American Androgen Antagonists Androgen Receptor Androgen Suppression Androgens Apoptosis Area Bicalutamide Biological Assay Cancer Biology Cancer Etiology Castration Cell Proliferation Cell Survival Cessation of life Clinical Clinical Research Clinical Treatment Clinical Trials Development Diagnosis Disease Resistance Disease regression Dutasteride Effectiveness Environment Epithelial Ethics Funding Gene Expression Genomics Goals Growth Heterogeneity Histologic Hormonal Hormones Individual Investigation Ketoconazole Localized Malignant Neoplasms Malignant neoplasm of prostate Measures Mediating Medical Mentors Mentorship Methods Molecular Neoadjuvant Therapy Pathway interactions Patients Physicians Positioning Attribute Production Prostate Prostate Cancer therapy Prostatectomy Prostatic Prostatic Neoplasms Puncture biopsy Randomized Reproduction spores Research Research Infrastructure Research Personnel Residual state Resistance Resources Reverse Transcriptase Polymerase Chain Reaction Sampling Serum Signal Transduction Source Stanolone Testicular Hormones Testing Testosterone Testosterone 5-alpha-Reductase Tissue Sample Tissues Translational Research Treatment Efficacy Tumor Biology Tumor Markers Universities Washington anticancer research base cancer cell career cell type cholestenone 5 alpha-reductase deprivation design experience hormone therapy in vivo interest killings men neoplastic neoplastic cell programs response statistics therapy design tumor

项目摘要

DESCRIPTION (provided by applicant): Project Summary: My long term goal is a career in translational research, focused on the molecular investigation and clinical treatment of prostate cancer. My immediate career goal is to develop the expertise in prostate cancer biology and clinical research that will allow me to pursue an independent career as a physician-investigator. Through a combination of didactics and mentored research experiences I will lay a groundwork in statistics, ethics, prostate tumor biology and clinical trial development that will position me to apply for and obtain funding in clinical research areas that will grow out of my current interests in the molecular effects of androgens on prostatic epithelial tissue. The research infrastructure of the Hutchinson Center and the University of Washington, the collaborative environment created by the Prostate SPORE and Program in Prostate Cancer Research, and the dual scientific and clinical mentorship provided by my mentors encompass all the resources I will need to successfully transition to an independent career. Establishing whether intraprostatic androgen levels can be suppressed to below a threshold at which essentially all prostate cancer cells undergo apoptosis has never been quantitatively addressed. In this proposal we will quantitative the pharmacologic and treatment efficacy of androgen lowering treatment strategies by measuring intraprostatic androgen levels in context of tissue and molecular correlates of tumor regression. Men with localized prostate cancer will be randomized to receive three months of neoadjuvant hormonal therapy with one of four treatments designed to progressively inhibit the androgen axis. Prostate samples obtained at diagnosis and prostatectomy will be assayed for treatment efficacy based on androgen levels, histological measures of tissue response, and assessment of androgen-regulated gene expression. Relevance: Prostate cancer is the most common cancer in American men, and the second leading cause of cancer-related death. Prostate cancer cells rely on the hormone testosterone for survival. Current methods of hormonal treatment only inhibit testicular hormone production, and ultimately fail to control the growth of prostate cancer cells. Our study will determine whether treatments inhibiting multiple sources of testosterone production (testicular, adrenal and prostatic) will be more effective than current methods in decreasing hormone levels inside the prostate, and therefore, more effective in killing prostate cancer cells.

描述（由申请人提供）：项目摘要：我的长期目标是从事转化研究，重点是前列腺癌的分子研究和临床治疗。我的近期职业目标是发展前列腺癌生物学和临床研究方面的专业知识，这将使我能够作为一名医生研究员追求独立的职业生涯。通过结合教学和指导研究经验，我将在统计学、伦理学、前列腺肿瘤生物学和临床试验开发方面奠定基础，这将使我能够申请并获得临床研究领域的资金，这些资金将源于我目前对以下领域的兴趣：雄激素对前列腺上皮组织的分子效应。哈钦森中心和华盛顿大学的研究基础设施、前列腺 SPORE 和前列腺癌研究计划创建的协作环境以及我的导师提供的双重科学和临床指导涵盖了我成功过渡到的所有资源。独立的职业生涯。确定前列腺内雄激素水平是否可以被抑制到低于基本上所有前列腺癌细胞都会发生凋亡的阈值尚未得到定量解决。在本提案中，我们将通过测量肿瘤消退的组织和分子相关性背景下的前列腺内雄激素水平来定量雄激素降低治疗策略的药理学和治疗效果。患有局限性前列腺癌的男性将被随机接受三个月的新辅助激素治疗，其中包括四种旨在逐渐抑制雄激素轴的治疗方法之一。将根据雄激素水平、组织反应的组织学测量以及雄激素调节基因表达的评估，对诊断和前列腺切除术中获得的前列腺样本进行治疗效果分析。相关性：前列腺癌是美国男性最常见的癌症，也是癌症相关死亡的第二大原因。前列腺癌细胞依靠睾酮激素来生存。目前的激素治疗方法只能抑制睾丸激素的产生，最终无法控制前列腺癌细胞的生长。我们的研究将确定抑制多种睾酮产生来源（睾丸、肾上腺和前列腺）的治疗是否比目前的方法更有效地降低前列腺内的激素水平，从而更有效地杀死前列腺癌细胞。