Elucidating Novel Mechanisms Underlying Prostate Cancer Development

项目摘要/摘要 前列腺癌是美国男性最常见的癌症。对患有慢性阻塞性肺病的男性的一线治疗 侵袭性前列腺癌是激素治疗或雄激素消融治疗。尽管最初的回应是 不幸的是，观察到这种疾病通常以侵袭性激素治疗抵抗的形式复发 被称为耐阉割前列腺癌(CRPC)。激素治疗难治性前列腺癌的现有治疗方法 癌症或CRPC只会延长患者的寿命几个月。因此，迫切需要确定 CRPC发生发展的分子机制并确定新的攻克策略 侵袭性前列腺癌。 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)研究Trop2参与攻击性人格发展的分子机制。 疾病。 2)开发新的抑制剂以阻断Trop2的功能，作为治疗晚期前列腺癌的新策略。 拟议项目的完成将导致确定新的治疗目标和发现新的治疗方法 治疗侵袭性前列腺癌。拟议的项目将开发新的治疗策略来抑制Trop2 侵袭性前列腺癌的受体在临床前环境中创建了重要的翻译联系 建议在不久的将来研究和治疗侵袭性前列腺癌患者。由于 Trop2在许多上皮性肿瘤中的高表达，我们相信我们的发现将适用于广泛的 癌症的范围。

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.