Elucidating the Role of Trop2 in Prostate Cancer

阐明 Trop2 在前列腺癌中的作用

基本信息

批准号：
10753382
负责人：
Tanya I Stoyanova
金额：
$ 35.23万
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：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10753382
关键词：
Advanced Development Aggressive Clinical Course Androgens Automobile Driving Binding Cancer Etiology Carcinoma Castration Cell Surface Proteins Cell surface Cells Cessation of life ChIP-seq Complex Development Disease Extracellular Domain Future Generations Genetic Transcription Goals Growth Human Incidence Invaded Knock-out Life Expectancy Link Longevity Maintenance Malignant Neoplasms Malignant neoplasm of prostate Membrane Glycoproteins Metastatic Prostate Cancer Molecular Neoplasm Metastasis Neurosecretory Systems Oncogenic Outcome Pathway interactions Patients Phenotype Pre-Clinical Model Proteins Receptor Activation Recurrence Relapse Research Resistance Role Signal Transduction Study Section Testing United States advanced disease advanced prostate cancer androgen deprivation therapy castration resistant prostate cancer hormone therapy in vivo in vivo evaluation inhibitor insight men migration mortality novel novel therapeutic intervention overexpression prostate cancer cell prostate cancer model prostate cancer progression prostate carcinogenesis receptor response therapeutic target therapy resistant transcription factor transcriptome sequencing tumor tumor growth tumorigenesis

项目摘要

PROJECT SUMMARY/ABSTRACT Prostate cancer is the second most common cancer in men in the United States. The first line of treatment for men with aggressive prostate cancer is hormone therapy or androgen ablation therapy. Although initial responses are observed, unfortunately, the disease commonly recurs in its aggressive hormone therapy- resistant form also known as castration resistant prostate cancer (CRPC). Current therapies for hormone therapy resistant prostate cancer or CRPC prolong the patients’ lifespan by only a few months. Thus, there is an urgent need to identify the molecular mechanisms underlying the development of CRPC in order to define new strategies to overcome aggressive prostate cancer. Trop2 is a cell surface protein that is found altered in multiple types of human cancers. Our recent studies demonstrate that Trop2 is a novel promising therapeutic target for aggressive prostate cancer due to its high expression in advanced prostate cancer and its oncogenic role in the disease. The goals of the proposed research are to: 1) Establish Trop2 activation as a driver of CRPC and assess its role in tumor maintenance. 2) Investigate the molecular mechanisms through which Trop2 contributes to the development of the aggressive disease. The completion of the proposed project will lead to defining new molecular mechanisms underlying the development of aggressive prostate cancer. The proposed project will evaluate the oncogenic role of Trop2 receptor and its activation in aggressive prostate cancer in pre-clinical models of prostate cancer creating an important translational link between the proposed research and treatment of patients with aggressive disease in the near future. Due to the high expression of Trop2 in many epithelial cancers, we believe that our findings will be applicable to a broad range of cancers.

项目摘要/摘要前列腺癌是美国男性中第二常见的癌症。第一条治疗患有侵略性前列腺癌的男性是马酮治疗或雄激素消融疗法。虽然是最初的不幸的是，观察到该疾病通常在其侵略性的赛马治疗中复发的反应 - 抗性形式也称为耐cuattration抗性前列腺癌（CRPC）。当前的马疗法耐药前列腺癌或CRPC仅将患者的寿命延长了几个月。那是迫切需要确定CRPC发展的基础机制以定义克服积极的前列腺癌的新策略。 Trop2是一种细胞表面蛋白，发现在多种类型的人类癌症中改变了。我们最近的研究证明trop2是一个新颖的有希望的侵略性前列腺癌的治疗靶标的晚期前列腺癌及其在疾病中的致癌作用中的表达。提议的目标研究是： 1）将Trop2激活作为CRPC的驱动力，并评估其在肿瘤维持中的作用。 2）研究trop2促进侵略性的分子机制疾病。拟议项目的完成将导致定义新的分子机制侵略性前列腺癌的发展。拟议的项目将评估trop2的致癌作用受体及其在侵略性前列腺癌中的激活在前列腺癌的临床前模型中产生拟议的研究与对侵略性疾病患者的治疗之间的重要翻译联系不久的将来。由于Trop2在许多上皮癌中的高表达，我们认为我们的发现将会适用于广泛的癌症。