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Elucidating Novel Mechanisms Underlying Prostate Cancer Development

阐明前列腺癌发展的新机制

基本信息

批准号：
9759850
负责人：
Tanya I Stoyanova
金额：
$ 7.98万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-08 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9759850
关键词：
Advanced Development Androgen Antagonists Automobile Driving Binding Biotin Cancer Etiology Carcinoma Cell Nucleus Cell Proliferation Cell Surface Proteins Cell surface Cessation of life Development Disease Extracellular Domain Future Generations Genetic Glycoproteins Goals Growth Human Immunotherapy In Vitro Libraries Link Longevity Malignant Neoplasms Malignant neoplasm of prostate Mass Spectrum Analysis Maximum Tolerated Dose Molecular Oncogenic Outcome Patients Prostate Prostatic Neoplasms Receptor Signaling Relapse Research Role Route Signal Transduction Study Section Testing Therapeutic Intervention Tissue Sample Unfavorable Clinical Outcome United States advanced disease aggressive therapy androgen deprivation therapy cancer cell castration resistant prostate cancer cell growth chemotherapeutic agent high throughput screening hormone therapy human tissue improved in vitro testing in vivo inhibitor/antagonist insight men migration new therapeutic target novel novel strategies novel therapeutic intervention novel therapeutics overexpression pre-clinical prostate carcinogenesis receptor response small molecule inhibitor taxane therapeutic target therapy resistant tumor tumor growth tumorigenesis

项目摘要

PROJECT SUMMARY/ABSTRACT Prostate cancer is the 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 and 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) Investigate the molecular mechanisms through which Trop2 contributes to the development of the aggressive disease. 2) Develop new inhibitors to block Trop2 function as a novel therapeutic strategy for advanced prostate cancer. The completion of the proposed project will lead to defining new therapeutic targets and uncover novel therapies for aggressive prostate cancer. The proposed project will develop new therapeutic strategies to inhibit Trop2 receptor in aggressive prostate cancer in pre-clinical settings creating an important translational link between the proposed research and the treatment of patients with aggressive prostate cancer 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.

项目总结/摘要前列腺癌是美国男性最常见的癌症。男性的第一线治疗侵袭性前列腺癌是激素疗法或雄激素消融疗法。虽然初步反应是不幸的是，观察到这种疾病通常以其积极的激素治疗抗性形式复发，称为去势抵抗性前列腺癌（CRPC）。激素治疗抵抗性前列腺的当前疗法癌症或CRPC只会延长患者的寿命几个月。因此，迫切需要查明 CRPC发展的分子机制，并确定新的策略，以克服侵袭性前列腺癌 Trop 2是一种细胞表面蛋白，在多种类型的人类癌症中发现改变。我们最近的研究证明Trop 2是一种新的有希望的治疗靶点，用于侵袭性前列腺癌，因为它的高在晚期前列腺癌中的表达及其在疾病中的致癌作用。拟议的目标研究的目的是： 1)研究Trop 2促进侵袭性肿瘤发展的分子机制。疾病 2)开发新的抑制剂阻断Trop 2功能作为晚期前列腺癌的新治疗策略。拟议项目的完成将导致定义新的治疗靶点和发现新的疗法治疗侵袭性前列腺癌拟议的项目将开发新的治疗策略，以抑制Trop 2 受体在临床前环境中的侵袭性前列腺癌中的作用，建议的研究和治疗患者的侵袭性前列腺癌在不久的将来。由于 Trop 2在许多上皮癌中的高表达，我们相信我们的发现将适用于广泛的一系列癌症。