Elucidating the Role of Trop2 in Prostate Cancer

项目概要/摘要 前列腺癌是美国男性第二常见的癌症。治疗的第一线 男性侵袭性前列腺癌是激素治疗或雄激素消融治疗。尽管最初 不幸的是，这种疾病通常在其积极的激素治疗中复发- 前列腺癌的另一种类型是去势抵抗型，也称为去势抵抗性前列腺癌（CRPC）。激素的当前疗法 治疗抵抗性前列腺癌或CRPC仅延长患者的寿命几个月。因此， 迫切需要确定CRPC发展的分子机制，以确定 治疗侵袭性前列腺癌的新策略。 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)确定Trop 2激活作为CRPC的驱动因素，并评估其在肿瘤维持中的作用。 2)研究Trop 2促进侵袭性肿瘤发展的分子机制。 疾病 该项目的完成将导致定义新的分子机制， 前列腺癌的发展。拟议的项目将评估Trop 2的致癌作用 受体及其在前列腺癌临床前模型中的活化， 在侵袭性疾病患者的拟议研究和治疗之间的重要转化联系， 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有助于 适用于广泛的癌症。

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.