Elucidating the Role of Trop2 in Prostate Cancer

项目摘要/摘要 前列腺癌是美国男性第二常见的癌症。治疗的第一线是 患有侵袭性前列腺癌的男性接受激素治疗或雄激素消融治疗。虽然最初 不幸的是，这种疾病通常在其积极的激素治疗中复发- 耐药型也称为耐去势前列腺癌(CRPC)。目前激素的治疗方法 耐药前列腺癌或CRPC只会延长患者的生命几个月。因此，有 迫切需要确定CRPC发生的分子机制，以便确定 克服侵袭性前列腺癌的新策略。 Trop2是一种细胞表面蛋白，在多种类型的人类癌症中发现发生改变。我们最近的研究 证明Trop2是一种新的有希望的治疗侵袭性前列腺癌的靶点。 晚期前列腺癌的表达及其致癌作用。建议的目标是 研究的目的是： 1)确定Trop2的激活是CRPC的驱动因素，并评估其在肿瘤维持中的作用。 2)探讨Trop2参与攻击性人格发展的分子机制。 疾病。 拟议项目的完成将导致定义新的分子机制 发生侵袭性前列腺癌。拟议的项目将评估trop2的致癌作用。 前列腺癌临床前模型中侵袭性前列腺癌的受体及其激活 拟议的研究和治疗侵袭性疾病患者之间的重要翻译联系 在不久的将来。由于Trop2在许多上皮性癌症中都有高表达，我们相信我们的发现将 适用于多种癌症。

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.